Academic Journal
Progress and new challenges in image-based profiling.
| Τίτλος: | Progress and new challenges in image-based profiling. |
|---|---|
| Συγγραφείς: | Serrano E; Department of Biomedical Informatics, University of Colorado Anschutz, Aurora, CO, USA., Peters J; Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI, USA., Wagner J; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom., Graham RE; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom., Chen Z; Calico Life Sciences, South San Francisco, CA, USA., Feng BY; Calico Life Sciences, South San Francisco, CA, USA., Miranda G; Department of Computational Science and Technology, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden., Kalinin AA; Imaging Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Vulliard L; Systems Immunology and Single-Cell Biology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Tomkinson J; Department of Biomedical Informatics, University of Colorado Anschutz, Aurora, CO, USA., Mattson C; Department of Biomedical Informatics, University of Colorado Anschutz, Aurora, CO, USA., Lippincott MJ; Department of Biomedical Informatics, University of Colorado Anschutz, Aurora, CO, USA., Kang Z; Research Program in Systems Oncology, University of Helsinki, Helsinki, Finland., Sitani D; Department of Systems Medicine, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany., Bunten D; Department of Biomedical Informatics, University of Colorado Anschutz, Aurora, CO, USA., Seal S; Imaging Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Carragher NO; Cancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom., Carpenter AE; Imaging Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Singh S; Imaging Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Marin Zapata PA; Bayer AG, Berlin, Germany., Caicedo JC; Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI, USA., Way GP; Department of Biomedical Informatics, University of Colorado Anschutz, Aurora, CO, USA. gregory.way@cuanschutz.edu. |
| Πηγή: | Molecular systems biology [Mol Syst Biol] 2026 May; Vol. 22 (5), pp. 624-658. Date of Electronic Publication: 2026 Mar 27. |
| Τύπος έκδοσης: | Journal Article; Review |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: EMBO Press Country of Publication: Germany NLM ID: 101235389 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1744-4292 (Electronic) Linking ISSN: 17444292 NLM ISO Abbreviation: Mol Syst Biol Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2024- : Heidelberg : EMBO Press Original Publication: London : Nature Pub. Group, c2005- |
| Ιατρικοί όροι (MeSH): | Image Processing, Computer-Assisted*/methods , Computational Biology*/methods , Single-Cell Analysis*/methods, Microscopy/methods ; Imaging, Three-Dimensional/methods ; Humans ; Deep Learning ; Software ; Animals ; Phenotype ; Reproducibility of Results |
| Περίληψη: | For over two decades, image-based profiling has revolutionized cell phenotype analysis. Image-based profiling processes rich, high-throughput, microscopy data into thousands of unbiased measurements that reveal phenotypic patterns powerful for drug discovery, functional genomics, and cell state classification. Here, we review the evolving computational landscape of image-based profiling, detailing the bioinformatics processes involved from feature extraction to normalization and batch correction. We discuss how deep learning has fundamentally reshaped the field. We examine key methodological advancements, such as single-cell analysis, the development of robust similarity metrics, and the expansion into new modalities like optical pooled screening, temporal imaging, and 3D organoid profiling. We also highlight the growth of public benchmarks and open-source software ecosystems as a key driver for fostering reproducibility and collaboration. Despite these advances, the field still faces substantial challenges, particularly in developing methods for emerging temporal and 3D data modalities, establishing robust quality control standards and workflows, and interpreting the processed features. By focusing on the technical evolution of image-based profiling rather than the wide-ranging biological applications, our aim with this review is to provide researchers with a roadmap for navigating the progress and new challenges in this rapidly advancing domain. (© 2026. The Author(s).) |
| Competing Interests: | Disclosure and competing interests statement. NOC is co-founder, shareholder, and management consultant for PhenoTherapeutics Ltd. SS and AEC serve as scientific advisors for companies that use image-based profiling and Cell Painting (AEC: Recursion, SyzOnc, Quiver Bioscience, SS: Waypoint Bio, Dewpoint Therapeutics, Deepcell) and receive honoraria for occasional scientific visits to pharmaceutical and biotechnology companies. The remaining authors declare no competing interests. |
| Σχόλια: | Update of: ArXiv. 2025 Aug 7:arXiv:2508.05800v1.. (PMID: 40799808) |
| References: | Aggarwal CC, Hinneburg A, Keim DA (2001) On the surprising behavior of distance metrics in high dimensional space. In: Database theory—ICDT 2001. Springer, Berlin Heidelberg, pp 420–434. Aghayev Z, Szafran AT, Tran A, Ganesh HS, Stossi F, Zhou L, Mancini MA, Pistikopoulos EN, Beykal B (2023) Machine learning methods for endocrine disrupting potential identification based on single-cell data. Chem Eng Sci 281:119086. (PMID: 10.1016/j.ces.2023.1190863763722710448728) Akbarzadeh M, Deipenwisch I, Schoelermann B, Pahl A, Sievers S, Ziegler S, Waldmann H (2022) Morphological profiling by means of the Cell Painting assay enables identification of tubulin-targeting compounds. Cell Chem Biol 29:1053–1064.e3. (PMID: 10.1016/j.chembiol.2021.12.00934968420) Aleksander SA, Balhoff J, Carbon S, Michael J, Drabkin HJ, Ebert D, Feuermann M, Gaudet P, Harris NL, Hill DP et al (2023) The Gene Ontology knowledgebase in 2023. Genetics 224:iyad031. (PMID: 10.1093/genetics/iyad0313686652910158837) Alieva M, Wezenaar AKL, Wehrens EJ, Rios AC (2023) Bridging live-cell imaging and next-generation cancer treatment. Nat Rev Cancer 23:731–745. (PMID: 10.1038/s41568-023-00610-537704740) Aras BS (2017) Investigation of some cell morphology using phase field method. Thesis, Ohio State University. Arevalo J, Su E, Ewald JD, van Dijk R, Carpenter AE, Singh S (2024) Evaluating batch correction methods for image-based cell profiling. Nat Commun 15:1–12. (PMID: 10.1038/s41467-024-50613-5) Arora A, Alderman JE, Palmer J, Ganapathi S, Laws E, McCradden MD, Oakden-Rayner L, Pfohl SR, Ghassemi M, McKay F et al (2023) The value of standards for health datasets in artificial intelligence-based applications. Nat Med 29:2929–2938. (PMID: 10.1038/s41591-023-02608-w3788462710667100) Auld DS, Peter A Coassin BS, Coussens NP, Hensley P, Klumpp-Thomas C, Michael S, Sitta Sittampalam G, Trask BS OJ, Wagner BK, Weidner JR et al (2020) Microplate selection and recommended practices in high-throughput screening and quantitative biology. In: Assay guidance manual [Internet]. Eli Lilly & Company and the National Center for Advancing Translational Sciences. Bae S, Na KJ, Koh J, Lee DS, Choi H, Kim YT (2022) CellDART: cell type inference by domain adaptation of single-cell and spatial transcriptomic data. Nucleic Acids Res 50:e57. (PMID: 10.1093/nar/gkac084351915039177989) Bao Y, Sivanandan S, Karaletsos T (2023) Channel vision transformers: an image is worth 1 ×16 × 16 words. Preprint at https://doi.org/10.48550/arXiv.2309.16108. Barteneva NS, Vorobjev IA (2015) Imaging flow cytometry: methods and protocols. Humana. Baysoy A, Bai Z, Satija R, Fan R (2023) The technological landscape and applications of single-cell multi-omics. Nat Rev Mol Cell Biol 24:695–713. (PMID: 10.1038/s41580-023-00615-w3728029610242609) Berg EL (2021) The future of phenotypic drug discovery. Cell Chem Biol 28:424–430. Berg S, Kutra D, Kroeger T, Straehle CN, Kausler BX, Haubold C, Schiegg M, Ales J, Beier T, Rudy M et al (2019) ilastik: interactive machine learning for (bio)image analysis. Nat Methods 16:1226–1232. (PMID: 10.1038/s41592-019-0582-931570887) Betge J, Rindtorff N, Sauer J, Rauscher B, Dingert C, Gaitantzi H, Herweck F, Srour-Mhanna K, Miersch T, Valentini E et al (2022) The drug-induced phenotypic landscape of colorectal cancer organoids. Nat Communs 13:1–15. Bian X, Li G, Wang C, Liu W, Lin X, Chen Z, Cheung M, Luo X (2021) A deep learning model for detection and tracking in high-throughput images of organoid. Comput Biol Med 134:104490. (PMID: 10.1016/j.compbiomed.2021.10449034102401) Bigverdi M, Hockendorf B, Yao H, Hanslovsky P, Lopez R, Richmond D (2024) Gene-level representation learning via interventional style transfer in optical pooled screening. Preprint at https://doi.org/10.48550/arXiv.2406.07763. Birmingham A, Selfors LM, Forster T, Wrobel D, Kennedy CJ, Shanks E, Santoyo-Lopez J, Dunican DJ, Long A, Kelleher D et al (2009) Statistical methods for analysis of high-throughput RNA interference screens. Nat Methods 6:569–575. (PMID: 10.1038/nmeth.1351196444582789971) Bock C, Datlinger P, Chardon F, Coelho MA, Dong MB, Lawson KA, Lu T, Maroc L, Norman TM, Song B et al (2022) High-content CRISPR screening. Nat Rev Methods Primers 2:1–23. (PMID: 10.1038/s43586-021-00093-4) Bommasani R, Hudson DA, Adeli E, Altman R, Arora S, von Arx S, Bernstein MS, Bohg J, Bosselut A, Brunskill E et al (2021) On the opportunities and risks of foundation models. Preprint at https://doi.org/10.48550/arXiv.2108.07258. Bond C, Santiago-Ruiz AN, Tang Q, Lakadamyali M (2022) Technological advances in super-resolution microscopy to study cellular processes. Mol Cell 82:315–332. (PMID: 10.1016/j.molcel.2021.12.022350630998852216) Borowa A, Rymarczyk D, Żyła M, Kańdula M, Sánchez-Fernández A, Rataj K, Struski Ł, Tabor J, Zieliński B (2024) Decoding phenotypic screening: A comparative analysis of image representations. Comput Struct Biotechnol J 23:1181–1188. (PMID: 10.1016/j.csbj.2024.02.0223851097610951426) Bourriez N, Bendidi I, Cohen E, Watkinson G, Sanchez M, Bollot G & Genovesio A (2024) ChAda-ViT : Channel adaptive attention for joint representation learning of heterogeneous microscopy image. In 2024 IEEE/CVF Conference on Computer Vision and Pattern Recognition (CVPR). IEEE, pp 11556–11565. Boyd JC, Pinheiro A, Del Nery E, Reyal F, Walter T (2019) Domain-invariant features for mechanism of action prediction in a multi-cell-line drug screen. Bioinformatics 36:1607–1613. (PMID: 10.1093/bioinformatics/btz774) Bozal SB, Sjogren G, Costa AP, Brown JS, Roberts S, Baker D, Gabriel P Jr, Ristau BT, Samuels M, Flynn WF et al (2024) Development of an automated 3D high content cell screening platform for organoid phenotyping. SLAS Discov 29:100182. (PMID: 10.1016/j.slasd.2024.1001823924518012380041) Bragantini J, Theodoro I, Zhao X, Huijben TAPM, Hirata-Miyasaki E, VijayKumar S, Balasubramanian A, Lao T, Agrawal R, Xiao S et al (2024) Ultrack: pushing the limits of cell tracking across biological scales. Nat Methods 22:2423–2436. Bray M-A, Carpenter AE (2018) Quality control for high-throughput imaging experiments using machine learning in CellProfiler. Methods Mol Biol 1683:89–112. (PMID: 10.1007/978-1-4939-7357-6_7290824896112602) Bray M-A, Gustafsdottir SM, Rohban MH, Singh S, Ljosa V, Sokolnicki KL, Bittker JA, Bodycombe NE, Dancík V, Hasaka TP et al (2017) A dataset of images and morphological profiles of 30,000 small-molecule treatments using the Cell Painting assay. Gigascience 6:1–5. (PMID: 10.1093/gigascience/giw014283279785721342) Bray M-A, Singh S, Han H, Davis CT, Borgeson B, Hartland C, Kost-Alimova M, Gustafsdottir SM, Gibson CC, Carpenter AE (2016) Cell Painting, a high-content image-based assay for morphological profiling using multiplexed fluorescent dyes. Nat Protocols 11:1757–1774. (PMID: 10.1038/nprot.2016.105275601785223290) Bunten D, Tomkinson J, Serrano E, Lippincott MJ, Brewer KI, Rubinetti V, Alquaddoomi F, Way GP (2025) Scalable data harmonization for single-cell image-based profiling with CytoTable. Preprint at bioRxiv https://doi.org/10.1101/2025.06.19.660613. Bushiri, Pwesombo D, Beese C, Schmied C, Sun H (2025) Semisupervised contrastive learning for bioactivity prediction using Cell Painting image data. J Chem Inf Model 65:528–543. (PMID: 10.1021/acs.jcim.4c00835) Caicedo JC, Arevalo J, Piccioni F, Bray M-A, Hartland CL, Wu X, Brooks AN, Berger AH, Boehm JS, Carpenter AE et al (2022) Cell painting predicts impact of lung cancer variants. Mol Biol Cell 33:ar49. Caicedo JC, Cooper S, Heigwer F, Warchal S, Qiu P, Molnar C, Vasilevich AS, Barry JD, Bansal HS, Kraus O et al (2017) Data-analysis strategies for image-based cell profiling. Nat Methods 14:849–863. (PMID: 10.1038/nmeth.4397288583386871000) Caicedo JC, McQuin C, Goodman A, Singh S, Carpenter AE (2018) Weakly supervised learning of single-cell feature embeddings. Proc IEEE Comput Soc Conf Comput Vis Pattern Recognit 2018:9309–9318. (PMID: 309184356432648) Caicedo JC, Singh S, Carpenter AE (2016) Applications in image-based profiling of perturbations. Curr Opin Biotechnol 39:134–142. Carlson RJ, Leiken MD, Guna A, Hacohen N, Blainey PC (2023) A genome-wide optical pooled screen reveals regulators of cellular antiviral responses. Proc Natl Acad Sci USA 120:e2210623120. (PMID: 10.1073/pnas.22106231203704353910120039) Caron M, Touvron H, Misra I, Jegou H, Mairal J, Bojanowski P & Joulin A (2021) Emerging properties in self-supervised vision transformers. In 2021 IEEE/CVF International Conference on Computer Vision (ICCV). IEEE. Carpenter AE, Jones TR, Lamprecht MR, Clarke C, Kang IH, Friman O, Guertin DA, Chang JH, Lindquist RA, Moffat J et al (2006) CellProfiler: image analysis software for identifying and quantifying cell phenotypes. Genome Biol 7:1–11. (PMID: 10.1186/gb-2006-7-10-r100) Cayuela López A, García-Cuesta EM, Gardeta SR, Rodríguez-Frade JM, Mellado M, Gómez-Pedrero JA, S Sorzano CO (2023) TrackAnalyzer: A Fiji/ImageJ toolbox for a holistic analysis of tracks. Biol Imaging 3:e18. (PMID: 10.1017/S2633903X230001813851017210951927) Celik S, Hütter J-C, Carlos SM, Lazar NH, Mohan R, Tillinghast C, Biancalani T, Fay MM, Earnshaw BA, Haque IS (2024) Building, benchmarking, and exploring perturbative maps of transcriptional and morphological data. PLoS Comput Biol 20:e1012463. (PMID: 10.1371/journal.pcbi.10124633935288811469686) Chai B, Efstathiou C, Yue H, Draviam VM (2024) Opportunities and challenges for deep learning in cell dynamics research. Trends Cell Biol 34:955–967. (PMID: 10.1016/j.tcb.2023.10.01038030542) Chandrasekaran SN, Ackerman J, Alix E, Ando DM, Arevalo J, Bennion M, Boisseau N, Borowa A, Boyd JD, Brino L et al (2023) JUMP Cell Painting dataset: morphological impact of 136,000 chemical and genetic perturbations. Preprint at bioRxiv https://doi.org/10.1101/2023.03.23.534023. Chandrasekaran SN, Alix E, Arevalo J, Borowa A, Byrne PJ, Charles WG, Chen ZS, Cimini BA, Deng B, Doench JG et al (2024a) Morphological map of under- and over-expression of genes in human cells. Nat Methods 22:1742–1752. Chandrasekaran SN, Ceulemans H, Boyd JD, Carpenter AE (2020) Image-based profiling for drug discovery: due for a machine-learning upgrade?. Nat Rev Drug Discov 20:145. (PMID: 10.1038/s41573-020-00117-w333539867754181) Chandrasekaran SN, Cimini BA, Goodale A, Miller L, Kost-Alimova M, Jamali N, Doench JG, Fritchman B, Skepner A, Melanson M et al (2024b) Three million images and morphological profiles of cells treated with matched chemical and genetic perturbations. Nat Methods 21:1114–1121. (PMID: 10.1038/s41592-024-02241-63859445211166567) Chelebian E, Avenel C, Wählby C (2025) Combining spatial transcriptomics with tissue morphology. Nat Commun 16:4452. (PMID: 10.1038/s41467-025-58989-84036046712075478) Chen B-C, Legant WR, Wang K, Shao L, Milkie DE, Davidson MW, Janetopoulos C, Wu XS, Hammer JA 3rd, Liu Z et al (2014) Lattice light-sheet microscopy: imaging molecules to embryos at high spatiotemporal resolution. Science 346:1257998. (PMID: 10.1126/science.1257998253428114336192) Chen C, Mat Isa NA, Liu X (2025) A review of convolutional neural network based methods for medical image classification. Comput Biol Med 185:109507. (PMID: 10.1016/j.compbiomed.2024.10950739631108) Chen H, Murphy RF (2023) Evaluation of cell segmentation methods without reference segmentations. Mol Biol Cell 34:ar50. (PMID: 10.1091/mbc.E22-08-036436515991) Chen J, Ding L, Viana MP, Lee H, Sluezwski MF, Morris B, Hendershott MC, Yang R, Mueller IA, Rafelski SM (2018) The Allen Cell and Structure Segmenter: a new open source toolkit for segmenting 3D intracellular structures in fluorescence microscopy images. Preprint at bioRxiv https://doi.org/10.1101/491035. Chen T, Kornblith S, Norouzi M, Hinton G (2020) A simple framework for contrastive learning of visual representations. Preprint at https://doi.org/10.48550/arXiv.2002.05709. Chen W, Guillaume-Gentil O, Rainer PY, Gäbelein CG, Saelens W, Gardeux V, Klaeger A, Dainese R, Zachara M, Zambelli T et al (2022) Live-seq enables temporal transcriptomic recording of single cells. Nature 608:733–740. (PMID: 10.1038/s41586-022-05046-9359781879402441) Chen Y, Song Y, Zhang C, Zhang F, O’Donnell L, Chrzanowski W, Cai W (2021a) Celltrack R-CNN: a novel end-to-end deep neural network for cell segmentation and tracking in microscopy images. In: 2021 IEEE 18th international symposium on biomedical imaging (ISBI). IEEE. Chen Z, Pham C, Wang S, Doron M, Moshkov N, Plummer BA, Caicedo JC (2023) CHAMMI: a benchmark for channel-adaptive models in microscopy imaging. Preprint at https://doi.org/10.48550/arXiv.2310.19224. Chen Z, Song S, Wei Z, Fang J, Long J (2021b) Approximating median absolute deviation with bounded error. Proc VLDB Endowment 14:2114–2126. (PMID: 10.14778/3476249.3476266) Christoforow A, Wilke J, Binici A, Pahl A, Ostermann C, Sievers S, Waldmann H (2019) Design, synthesis, and phenotypic profiling of pyrano-furo-pyridone pseudo natural products. Angew Chem Int Ed Engl 58:14715–14723. (PMID: 10.1002/anie.201907853313396207687248) Cimini BA, Chandrasekaran SN, Kost-Alimova M, Miller L, Goodale A, Fritchman B, Byrne P, Garg S, Jamali N, Logan DJ et al (2023) Optimizing the Cell Painting assay for image-based profiling. Nat Protocols 18:1981–2013. (PMID: 10.1038/s41596-023-00840-93734460810536784) Cimini BA, Way G, Becker T, Weisbart E, Chandrasekaran SN, Tromans-Coia C, Shafqat Abbasi H, Carpenter A, Singh S (2019) Image-based profiling handbook. Github. Cole MB, Risso D, Wagner A, DeTomaso D, Ngai J, Purdom E, Dudoit S, Yosef N (2019) Performance assessment and selection of normalization procedures for single-cell RNA-seq. Cell Syst 8:315–328.e8. (PMID: 10.1016/j.cels.2019.03.010310223736544759) Corsello SM, Bittker JA, Liu Z, Gould J, McCarren P, Hirschman JE, Johnston SE, Vrcic A, Wong B, Khan M et al (2017) The drug repurposing hub: a next-generation drug library and information resource. Nat Med 23:405–408. (PMID: 10.1038/nm.4306283886125568558) Cottet M, Marrero YF, Mathien S, Audette K, Lambert R, Bonneil E, Chng K, Campos A, Andrews DW (2023) Live cell painting: new nontoxic dye to probe cell physiology in high content screening. SLAS Discov 29:100121. (PMID: 10.1016/j.slasd.2023.10.005) Cross-Zamirski JO, Anand P, Williams G, Mouchet E, Wang Y & Schönlieb C-B (2023) Class-guided image-to-image diffusion: Cell painting from Brightfield images with class labels. In 2023 IEEE/CVF International Conference on Computer Vision Workshops (ICCVW). IEEE, pp 3802–3811. Cross-Zamirski JO, Mouchet E, Williams G, Schönlieb C-B, Turkki R, Wang Y (2022) Label-free prediction of cell painting from brightfield images. Sci Rep 12:1–13. (PMID: 10.1038/s41598-022-12914-x) Cuccarese MF, Earnshaw BA, Heiser K, Fogelson B, Davis CT, McLean PF, Gordon HB, Skelly K-R, Weathersby FL, Rodic V et al (2020) Functional immune mapping with deep-learning enabled phenomics applied to immunomodulatory and COVID-19 drug discovery. Preprint at bioRxiv https://doi.org/10.1101/2020.08.02.233064. Dagher M, Ongo G, Robichaud N, Kong J, Rho W, Teahulos I, Tavakoli A, Bovaird S, Merjaneh S, Tan A et al (2025) nELISA: a high-throughput, high-plex platform enables quantitative profiling of the inflammatory secretome. Nat Methods 22:2375–2385. Dahlin JL, Hua BK, Zucconi BE, Nelson SD, Singh S, Carpenter AE, Shrimp JH, Lima-Fernandes E, Wawer MJ, Chung LPW et al (2023) Reference compounds for characterizing cellular injury in high-content cellular morphology assays. Nat Commun 14:1–16. (PMID: 10.1038/s41467-023-36829-x) Dai S, Xu Q, Wen P, Liu Y, Huang Q (2025) Self-supervised representation learning with local aggregation for image-based profiling. Preprint at https://doi.org/10.48550/arXiv.2506.14265. Danial JSH (2025) Super-resolution microscopy for structural biology. Nat Methods 22:1636–1652. (PMID: 10.1038/s41592-025-02731-140579628) Danino R, Nachman I, Sharan R (2024) Batch correction of single-cell sequencing data via an autoencoder architecture. Bioinform Adv 4:vbad186. (PMID: 10.1093/bioadv/vbad18638213820) Dao D, Fraser AN, Hung J, Ljosa V, Singh S, Carpenter AE (2016) CellProfiler analyst: interactive data exploration, analysis and classification of large biological image sets. Bioinformatics 32:3210–3212. De Lorenci AV, Yi SE, Moutakanni T, Bojanowski P, Couprie C, Caicedo JC, Pernice WMA (2024) Scaling channel-invariant self-supervised learning. De Donno C, Hediyeh-Zadeh S, Moinfar AA, Wagenstetter M, Zappia L, Lotfollahi M, Theis FJ (2023) Population-level integration of single-cell datasets enables multi-scale analysis across samples. Nat Methods 20:1683–1692. (PMID: 10.1038/s41592-023-02035-23781398910630133) De Vries M, Dent LG, Curry N, Rowe-Brown L, Bousgouni V, Fourkioti O, Naidoo R, Sparks H, Tyson A, Dunsby C et al (2025) Geometric deep learning and multiple-instance learning for 3D cell-shape profiling. Cell Syst 16:101229. (PMID: 10.1016/j.cels.2025.10122940112779) Dee W, Sequeira I, Lobley A, Slabaugh G (2024) Cell-vision fusion: A Swin transformer-based approach for predicting kinase inhibitor mechanism of action from Cell Painting data. iScience 27:110511. (PMID: 10.1016/j.isci.2024.1105113917577811340608) Dekkers JF, Alieva M, Cleven A, Keramati F, Wezenaar AKL, van Vliet EJ, Puschhof J, Brazda P, Johanna I, Meringa AD et al (2022) Uncovering the mode of action of engineered T cells in patient cancer organoids. Nat Biotechnol 41:60–69. (PMID: 10.1038/s41587-022-01397-w358793619849137) Dent LG, Curry N, Sparks H, Bousgouni V, Maioli V, Kumar S, Munro I, Butera F, Jones I, Arias-Garcia M et al (2024) Environmentally dependent and independent control of 3D cell shape. Cell Rep 43:114016. (PMID: 10.1016/j.celrep.2024.11401638636520) Di Bernardo M, Kern RS, Mallar A, Nutter-Upham A, Blainey PC, Cheeseman I (2025) Brieflow: an integrated computational pipeline for high-throughput analysis of optical pooled screening data. Preprint at bioRxiv https://doi.org/10.1101/2025.05.26.656231. Di Tommaso P, Chatzou M, Floden EW, Barja PP, Palumbo E, Notredame C (2017) Nextflow enables reproducible computational workflows. Nat Biotechnol 35:316–319. (PMID: 10.1038/nbt.382028398311) Diosdi A, Toth T, Harmati M, Istvan G, Schrettner B, Hapek N, Kovacs F, Kriston A, Buzas K, Pampaloni F et al (2025) HCS-3DX, a next-generation AI-driven automated 3D-oid high-content screening system. Nat Commun 16:8897. Djaffardjy M, Marchment G, Sebe C, Blanchet R, Bellajhame K, Gaignard A, Lemoine F, Cohen-Boulakia S (2023) Developing and reusing bioinformatics data analysis pipelines using scientific workflow systems. Comput Struct Biotechnol J 21:2075–2085. (PMID: 10.1016/j.csbj.2023.03.0033696801210030817) Doan M, Barnes C, McQuin C, Caicedo JC, Goodman A, Carpenter AE, Rees P (2021) Deepometry, a framework for applying supervised and weakly supervised deep learning to imaging cytometry. Nat Protoc 16:3572–3595. (PMID: 10.1038/s41596-021-00549-7341454348506936) Dong Y, Li D, Zheng Z, Zhou J (2022) Reproducible feature selection in high-dimensional accelerated failure time models. Stat Probab Lett 181:109275. (PMID: 10.1016/j.spl.2021.109275) Donovan-Maiye RM, Brown JM, Chan CK, Ding L, Yan C, Gaudreault N, Theriot JA, Maleckar MM, Knijnenburg TA, Johnson GR (2022) A deep generative model of 3D single-cell organization. PLoS Comput Biol 18:e1009155. (PMID: 10.1371/journal.pcbi.1009155350416518797242) Doron M, Moutakanni T, Chen ZS, Moshkov N, Caron M, Touvron H, Bojanowski P, Pernice WM, Caicedo JC (2023) Unbiased single-cell morphology with self-supervised vision transformers. Preprint at bioRxiv https://doi.org/10.1101/2023.06.16.545359. Dosovitskiy A, Beyer L, Kolesnikov A, Weissenborn D, Zhai X, Unterthiner T, Dehghani M, Minderer M, Heigold G, Gelly S et al (2020) An image is worth 16×16 words: transformers for image recognition at scale. Preprint at https://doi.org/10.48550/arXiv.2010.11929. Driscoll MK, Zaritsky A (2021) Data science in cell imaging. J Cell Sci 134:jcs254292. Durbin BP, Hardin JS, Hawkins DM, Rocke DM (2002) A variance-stabilizing transformation for gene-expression microarray data. Bioinformatics 18:S105–S110. (PMID: 10.1093/bioinformatics/18.suppl_1.S10512169537) Edlund C, Jackson TR, Khalid N, Bevan N, Dale T, Dengel A, Ahmed S, Trygg J, Sjögren R (2021) LIVECell-A large-scale dataset for label-free live cell segmentation. Nat Methods 18:1038–1045. (PMID: 10.1038/s41592-021-01249-6344625948440198) Edwards SJ, Carannante V, Kuhnigk K, Ring H, Tararuk T, Hallböök F, Blom H, Önfelt B, Brismar H (2020) High-resolution imaging of tumor spheroids and organoids enabled by expansion microscopy. Front Mol Biosci 7:208. (PMID: 10.3389/fmolb.2020.00208331953987543521) Eismann B, Krieger TG, Beneke J, Bulkescher R, Adam L, Erfle H, Herrmann C, Eils R, Conrad C (2020) Automated 3D light-sheet screening with high spatiotemporal resolution reveals mitotic phenotypes. J Cell Sci 133:jcs245043. (PMID: 10.1242/jcs.245043322958477286290) Elliott RJR, Nagle P, Furqan M, Dawson JC, McCarthy A, Munro AF, Drake C, Morrison GM, Marand M, Ebner D et al (2024) A comprehensive pharmacological survey across heterogeneous patient-derived GBM stem cell models. Preprint at bioRxiv https://doi.org/10.1101/2024.11.27.625719. Elmalam N, Ben Nedava L, Zaritsky A (2024) In silico labeling in cell biology: Potential and limitations. Curr Opin Cell Biol 89:102378. (PMID: 10.1016/j.ceb.2024.10237838838549) Ericsson L, Gouk H, Loy CC, Hospedales TM (2021) Self-supervised representation learning: introduction, advances and challenges. In IEEE Signal Processing Magazine, Vol. 39, pp 42--62. https://doi.org/10.1109/MSP.2021.3134634. Ershov D, Phan M-S, Pylvänäinen JW, Rigaud SU, Le Blanc L, Charles-Orszag A, Conway JRW, Laine RF, Roy NH, Bonazzi D et al (2022) TrackMate 7: integrating state-of-the-art segmentation algorithms into tracking pipelines. Nat Methods 19:829–832. (PMID: 10.1038/s41592-022-01507-135654950) Etherington TR (2021) Mahalanobis distances for ecological niche modelling and outlier detection: implications of sample size, error, and bias for selecting and parameterising a multivariate location and scatter method. PeerJ 9:e11436. (PMID: 10.7717/peerj.11436340263698121071) Ewald JD, Titterton KL, Bäuerle A, Beatson A, Boiko DA, Cabrera ÁA, Cheah J, Cimini BA, Gorissen B, Jones T et al (2025) Cell Painting for cytotoxicity and mode-of-action analysis in primary human hepatocytes. Preprint at bioRxiv https://doi.org/10.1101/2025.01.22.634152. Fay MM, Kraus O, Victors M, Arumugam L, Vuggumudi K, Urbanik J, Hansen K, Celik S, Cernek N, Jagannathan G et al (2023) RxRx3: phenomics map of biology. Preprint at bioRxiv https://doi.org/10.1101/2023.02.07.527350. Feldman D, Singh A, Schmid-Burgk JL, Carlson RJ, Mezger A, Garrity AJ, Zhang F, Blainey PC (2019) Optical Pooled Screens in Human Cells. Cell 179:787–799.e17. (PMID: 10.1016/j.cell.2019.09.016316267756886477) Follain G, Ghimire S, Pylvänäinen JW, Vaitkevičiūtė M, Hidalgo-Cenalmor I, Wurzinger D, Guzmán C, Conway JRW, Dibus M, Härkönen J et al (2026) Fast label-free live imaging with FlowVision reveals key principles of cancer cell arrest on endothelial monolayers. EMBO J 45:1381–1421. Fonnegra R, Sanian M, Chen Z, Paavolainen L, Caicedo J (2023) Analysis of cellular phenotypes with unbiased image-based generative models. In: NeurIPS 2023 generative AI and biology (GenBio) workshop. Foroughi Pour A, White BS, Park J, Sheridan TB, Chuang JH (2022) Deep learning features encode interpretable morphologies within histological images. Sci Rep 12:9428. (PMID: 10.1038/s41598-022-13541-2356763959177767) Frey B, Holmberg D, Byström P, Bergman E, Georgiev P, Johansson M, Hennig P, Rietdijk J, Rosén D, Carreras-Puigvert J et al (2025) Single-cell morphological profiling reveals insights into cell death. Preprint at bioRxiv https://doi.org/10.1101/2025.01.15.633042. Forsgren E, Cloarec O, Jonsson P, Lovell G, Trygg J (2024) A scalable, data analytics workflow for image-based morphological profiles. Chemometr Intell Lab Syst 254:105232. (PMID: 10.1016/j.chemolab.2024.105232) Funk L, Su K-C, Ly J, Feldman D, Singh A, Moodie B, Blainey PC, Cheeseman IM (2022) The phenotypic landscape of essential human genes. Cell 185:4634–4653.e22. (PMID: 10.1016/j.cell.2022.10.0173634725410482496) Gao X, Zhang F, Guo X, Yao M, Wang X, Chen D, Zhang G, Wang X, Lai L (2025a) Attention-based deep learning for accurate cell image analysis. Sci Rep 15:1–13. Gao Y, Zhang J, Wei S, Li Z (2025b) PFormer: An efficient CNN-Transformer hybrid network with content-driven P-attention for 3D medical image segmentation. Biomed Signal Process Control 101:107154. (PMID: 10.1016/j.bspc.2024.107154) Garcia-Fossa F, Cruz MC, Haghighi M, de Jesus MB, Singh S, Carpenter AE, Cimini BA (2023) Interpreting Image-based Profiles using Similarity Clustering and Single-Cell Visualization. Curr Protoc 3:e713. Garcia-Fossa F, Moraes-Lacerda T, Rodrigues-da-Silva M, Diaz-Rohrer B, Singh S, Carpenter AE, Cimini BA, de Jesus MB (2025) Live-cell painting: Image-based profiling in live cells using acridine orange. Mol Biol Cell 36:mr7. Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B et al (2012) ChEMBL: a large-scale bioactivity database for drug discovery. Nucleic Acids Res 40:D1100–D1107. (PMID: 10.1093/nar/gkr77721948594) Geng R, Kidder BL (2025) Automated image-based profiling of pluripotent stem cell colonies. Preprint at bioRxiv https://doi.org/10.1101/2025.09.16.676586. German Y, Vulliard L, Kamnev A, Pfajfer L, Huemer J, Mautner A-K, Rubio A, Kalinichenko A, Boztug K, Ferrand A et al (2021) Morphological profiling of human T and NK lymphocytes by high-content cell imaging. Cell Rep 36:109318. (PMID: 10.1016/j.celrep.2021.10931834233185) Giurgiu M, Reinhard J, Brauner B, Dunger-Kaltenbach I, Fobo G, Frishman G, Montrone C, Ruepp A (2018) CORUM: the comprehensive resource of mammalian protein complexes—2019. Nucleic Acids Res 47:D559–D563. (PMID: 10.1093/nar/gky973) Gladkova C, Paez-Segala MG, Grant WP, Myers SA, Wang Y, Vale RD (2024) A molecular switch for stress-induced activation of retrograde mitochondrial transport. Preprint at bioRxiv https://doi.org/10.1101/2024.09.13.612963. Godinez WJ, Hossain I, Lazic SE, Davies JW, Zhang X (2017) A multi-scale convolutional neural network for phenotyping high-content cellular images. Bioinformatics 33:2010–2019. (PMID: 10.1093/bioinformatics/btx06928203779) Goglia AG, Wilson MZ, Jena SG, Silbert J, Basta LP, Devenport D, Toettcher JE (2020) A live-cell screen for altered Erk dynamics reveals principles of proliferative control. Cell Syst 10:240–253.e6. (PMID: 10.1016/j.cels.2020.02.005321918747540725) Goldsborough P, Pawlowski N, Caicedo JC, Singh S, Carpenter AE (2017) CytoGAN: generative modeling of cell images. Preprint at bioRxiv https://doi.org/10.1101/227645. Gopalakrishnan V, Ma J & Xie Z (2024) Grad-CAMO: Learning interpretable single-cell morphological profiles from 3D cell painting images. In 2024 IEEE/CVF Conference on Computer Vision and Pattern Recognition Workshops (CVPRW). IEEE, pp 6988–6996. Gordonov S, Hwang MK, Wells A, Gertler FB, Lauffenburger DA, Bathe M (2016) Time series modeling of live-cell shape dynamics for image-based phenotypic profiling. Integr Biol 8:73–90. (PMID: 10.1039/C5IB00283D) Graham RE, Zheng R, Wagner J, Unciti-Broceta A, Hay DC, Forbes SJ, Gadd VL, Carragher NO (2025) Single-cell morphological tracking of cell states to identify small-molecule modulators of liver differentiation. iScience 28:111871. (PMID: 10.1016/j.isci.2025.1118713999586811848441) Gu J, Iyer A, Wesley B, Taglialatela A, Leuzzi G, Hangai S, Decker A, Gu R, Klickstein N, Shuai Y et al (2023) CRISPRmap: sequencing-free optical pooled screens mapping multi-omic phenotypes in cells and tissue. Preprint at bioRxiv https://doi.org/10.1101/2023.12.26.572587. Gu J, Iyer A, Wesley B, Taglialatela A, Leuzzi G, Hangai S, Decker A, Gu R, Klickstein N, Shuai Y et al (2024) Mapping multimodal phenotypes to perturbations in cells and tissue with CRISPRmap. Nat Biotechnol 43:1101–1115. Guo M, Wu Y, Hobson CM, Su Y, Qian S, Krueger E, Christensen R, Kroeschell G, Bui J, Chaw M et al (2025) Deep learning-based aberration compensation improves contrast and resolution in fluorescence microscopy. Nat Commun 16:313. (PMID: 10.1038/s41467-024-55267-x3974782411697233) Guo T, Chen Y, Shi M, Li X, Zhang MQ (2022) Integration of single cell data by disentangled representation learning. Nucleic Acids Res 50:e8. (PMID: 10.1093/nar/gkab978348500928788944) Gupta A, Wefers Z, Kahnert K, Hansen JN, Leineweber W, Cesnik A, Lu D, Axelsson U, Navarro FB, Karaletsos T et al (2024) SubCell: vision foundation models for microscopy capture single-cell biology. Preprint at bioRxiv https://doi.org/10.1101/2024.12.06.627299. Gupta S, Thakar U, Tokekar S (2025) A comprehensive survey on techniques for numerical similarity measurement. Expert Syst Appl 277:127235. (PMID: 10.1016/j.eswa.2025.127235) Haase C, Gustafsson K, Mei S, Yeh S-C, Richter D, Milosevic J, Turcotte R, Kharchenko PV, Sykes DB, Scadden DT et al (2022) Image-seq: spatially resolved single-cell sequencing guided by in situ and in vivo imaging. Nat Methods 19:1622–1633. (PMID: 10.1038/s41592-022-01673-2364244419718684) Haghighi M, Caicedo JC, Cimini BA, Carpenter AE, Singh S (2022) High-dimensional gene expression and morphology profiles of cells across 28,000 genetic and chemical perturbations. Nat Methods 19:1550–1557. (PMID: 10.1038/s41592-022-01667-03634483410012424) Haghverdi L, Lun ATL, Morgan MD, Marioni JC (2018) Batch effects in single-cell RNA-sequencing data are corrected by matching mutual nearest neighbors. Nat Biotechnol 36:421–427. (PMID: 10.1038/nbt.4091296081776152897) Haslum JF, Matsoukas C, Leuchowius K-J, Müllers E, Smith K (2022) Metadata-guided consistency learning for high content images. Preprint at https://doi.org/10.48550/arXiv.2212.11595. Haslum JF, Matsoukas C, Leuchowius K-J, Smith K (2024) Bridging generalization gaps in high content imaging through online self-supervised domain adaptation. In 2024 IEEE/CVF Winter Conference on Applications of Computer Vision (WACV). IEEE, pp 7723–7732. He K, Chen X, Xie S, Li Y, Dollar P, Girshick R (2022) Masked autoencoders are scalable vision learners. In 2022 IEEE/CVF conference on computer vision and pattern recognition (CVPR). IEEE. He K, Gkioxari G, Dollar P, Girshick R (2017) Mask R-CNN. In 2017 IEEE International Conference on Computer Vision (ICCV). IEEE. He K, Zhang X, Ren S, Sun J (2016) Deep residual learning for image recognition. In: 2016 IEEE conference on computer vision and pattern recognition (CVPR). IEEE, pp 770–778. Heigwer F, Scheeder C, Bageritz J, Yousefian S, Rauscher B, Laufer C, Beneyto-Calabuig S, Funk MC, Peters V, Boulougouri M et al (2023) A global genetic interaction network by single-cell imaging and machine learning. Cell Syst 14:346–362.e6. (PMID: 10.1016/j.cels.2023.03.0033711649810206407) Heiser K, McLean PF, Davis CT, Fogelson B, Gordon HB, Jacobson P, Hurst B, Miller B, Alfa RW, Earnshaw BA et al (2020) Identification of potential treatments for COVID-19 through artificial intelligence-enabled phenomic analysis of human cells infected with SARS-CoV-2. Preprint at bioRxiv https://doi.org/10.1101/2020.04.21.054387. Hie B, Bryson B, Berger B (2019) Efficient integration of heterogeneous single-cell transcriptomes using scanorama. Nat Biotechnol 37:685–691. (PMID: 10.1038/s41587-019-0113-3310614826551256) Hofmarcher M, Rumetshofer E, Clevert D-A, Hochreiter S, Klambauer G (2019) Accurate prediction of biological assays with high-throughput microscopy images and convolutional networks. J Chem Inf Model 59:1163–1171. (PMID: 10.1021/acs.jcim.8b0067030840449) Högel-Starck C, Timonen VA, Atarsaikhan G, Mogollon I, Polso M, Hassinen A, Honkanen J, Soini J, Ruokoranta T, Ahlnäs T et al (2024) Morphological single-cell analysis of peripheral blood mononuclear cells from 390 healthy blood donors with blood cell painting. Preprint at bioRxiv https://doi.org/10.1101/2024.05.17.594648. Holme B, Bjørnerud B, Pedersen NM, de la Ballina LR, Wesche J, Haugsten EM (2023) Automated tracking of cell migration in phase contrast images with CellTraxx. Sci Rep 13:22982. (PMID: 10.1038/s41598-023-50227-93815151410752880) Hörst F, Rempe M, Becker H, Heine L, Keyl J, Kleesiek J (2026) CellViT++: Energy-efficient and adaptive cell segmentation and classification using foundation models. Comput Methods Programs Biomed 277:109206. Hörst F, Rempe M, Heine L, Seibold C, Keyl J, Baldini G, Ugurel S, Siveke J, Grünwald B, Egger J et al (2024) CellViT: vision transformers for precise cell segmentation and classification. Med Image Anal 94:103143. (PMID: 10.1016/j.media.2024.10314338507894) Hotelling H (1936) Relations between two sets of variates. Biometrika 28:321. (PMID: 10.1093/biomet/28.3-4.321) Hu B, Canon S, Eloe-Fadrosh EA, Anubhav, Babinski M, Corilo Y, Davenport K, Duncan WD, Fagnan K, Flynn M et al (2021) Challenges in bioinformatics workflows for processing microbiome omics data at scale. Front Bioinform 1:826370. (PMID: 10.3389/fbinf.2021.82637036303775) Hu H, Sanghi S, Quon G (2025) Predicting emergent phenotypes from single cell populations using CELLECTION. Preprint at bioRxiv https://doi.org/10.1101/2025.09.02.673886. Hua SBZ, Lu AX, Moses AM (2021) CytoImageNet: a large-scale pretraining dataset for bioimage transfer learning. Preprint at https://doi.org/10.48550/arXiv.2111.11646. Huang G, Liu Z, Van Der Maaten L, Weinberger KQ (2017) Densely connected convolutional networks. In 2017 IEEE Conference on Computer Vision and Pattern Recognition (CVPR). IEEE. Huang J, Yuan C, Jiang J, Chen J, Badve SS, Gokmen-Polar Y, Segura RL, Yan X, Lazar A, Gao J et al (2025) Bridging cell morphological behaviors and molecular dynamics in multi-modal spatial omics with MorphLink. Nat Commun 16:5878. Huang K, Li M, Li Q, Chen Z, Zhang Y, Gu Z (2024) Image-based profiling and deep learning reveal morphological heterogeneity of colorectal cancer organoids. Comput Biol Med 173:108322. (PMID: 10.1016/j.compbiomed.2024.10832238554658) Huber W, von Heydebreck A, Sültmann H, Poustka A, Vingron M (2002) Variance stabilization applied to microarray data calibration and to the quantification of differential expression. Bioinformatics 18:S96–S104. (PMID: 10.1093/bioinformatics/18.suppl_1.S9612169536) Hughes RE, Elliott RJR, Munro AF, Makda A, O’Neill JR, Hupp T, Carragher NO (2020) High-content phenotypic profiling in esophageal adenocarcinoma identifies selectively active pharmacological classes of drugs for repurposing and chemical starting points for novel drug discovery. SLAS Discov 25:770–782. (PMID: 10.1177/2472555220917115324411817372582) Hur SW, Kwon M, Manoharaan R, Mohammadi MH, Samuel AZ, Mulligan MP, Hergenrother PJ, Bhargava R (2024) Capturing cell morphology dynamics with high temporal resolution using single-shot quantitative phase gradient imaging. J Biomed Opt 29:S22712. (PMID: 10.1117/1.JBO.29.S2.S227123901551011249975) Hutz JE, Nelson T, Wu H, McAllister G, Moutsatsos I, Jaeger SA, Bandyopadhyay S, Nigsch F, Cornett B, Jenkins JL et al (2013) The multidimensional perturbation value: a single metric to measure similarity and activity of treatments in high-throughput multidimensional screens. J Biomol Screen 18:367–377. Ichita M, Yamamichi H, Higaki T (2025) Virtual staining from bright-field microscopy for label-free quantitative analysis of plant cell structures. Plant Mol Biol 115:29. (PMID: 10.1007/s11103-025-01558-w3988509511782351) Jacques M-A, Dobrzyński M, Gagliardi PA, Sznitman R, Pertz O (2021) CODEX, a neural network approach to explore signaling dynamics landscapes. Mol Syst Biol 17:e10026. (PMID: 10.15252/msb.202010026338357018034356) Janse RJ, Hoekstra T, Jager KJ, Zoccali C, Tripepi G, Dekker FW, van Diepen M (2021) Conducting correlation analysis: important limitations and pitfalls. Clin Kidney J 14:2332–2337. (PMID: 10.1093/ckj/sfab085347544288572982) Janssens R, Zhang X, Kauffmann A, de Weck A, Durand EY (2021) Fully unsupervised deep mode of action learning for phenotyping high-content cellular images. Bioinformatics 37:4548–4555. (PMID: 10.1093/bioinformatics/btab49734240099) Jeremiasse B, van Ineveld RL, Bok V, Kleinnijenhuis M, de Blank S, Alieva M, Johnson HR, van Vliet EJ, Zeeman AL, Wellens LM et al (2024) A multispectral 3D live organoid imaging platform to screen probes for fluorescence guided surgery. EMBO Mol Med 16:1495–1514. (PMID: 10.1038/s44321-024-00084-43883113111251264) Ji Y, Tejada-Lapuerta A, Schmacke NA, Zheng Z, Zhang X, Khan S, Rothenaigner I, Tschuck J, Hadian K, Theis FJ (2024) Scalable and universal prediction of cellular phenotypes. Preprint at bioRxiv https://doi.org/10.1101/2024.08.12.607533. Jiang X, Wang S, Guo L, Zhu B, Wen Z, Jia L, Xu L, Xiao G, Li Q (2024) iIMPACT: integrating image and molecular profiles for spatial transcriptomics analysis. Genome Biol 25:1–25. (PMID: 10.1186/s13059-024-03289-5) Johnson WE, Li C, Rabinovic A (2007) Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics 8:118–127. (PMID: 10.1093/biostatistics/kxj03716632515) Kalinin AA, Arevalo J, Serrano E, Vulliard L, Tsang H, Bornholdt M, Muñoz AF, Sivagurunathan S, Rajwa B, Carpenter AE et al (2025) A versatile information retrieval framework for evaluating profile strength and similarity. Nat Commun 16:5181. Keefe CR, Dillon MR, Gehret E, Herman C, Jewell M, Wood CV, Bolyen E, Caporaso JG (2023) Facilitating bioinformatics reproducibility with QIIME 2 Provenance Replay. PLoS Comput Biol 19:e1011676. Kelley ME, Berman AY, Stirling DR, Cimini BA, Han Y, Singh S, Carpenter AE, Kapoor TM, Way GP (2023) High-content microscopy reveals a morphological signature of bortezomib resistance. Elife 12:e91362. Kenyon-Dean K, Wang ZJ, Urbanik J, Donhauser K, Hartford J, Saberian S, Sahin N, Bendidi I, Celik S, Fay M et al (2024) ViTally consistent: scaling biological representation learning for cell microscopy. Preprint at https://doi.org/10.48550/arXiv.2411.02572. Kessy A, Lewin A, Strimmer K (2018) Optimal whitening and decorrelation. Am Stat 72:309–314. (PMID: 10.1080/00031305.2016.1277159) Kim V, Adaloglou N, Osterland M, Morelli FM, Halawa M, König T, Gnutt D, Marin Zapata PA (2025) Self-supervision advances morphological profiling by unlocking powerful image representations. Sci Rep 15:1–15. Kobayashi H, Cheveralls KC, Leonetti MD, Royer LA (2022) Self-supervised deep learning encodes high-resolution features of protein subcellular localization. Nat Methods 19:995–1003. (PMID: 10.1038/s41592-022-01541-z358796089349041) Kochetov B, Uttam S (2024) Local mean suppression filter for effective background identification in fluorescence images. Preprint at bioRxiv https://doi.org/10.1101/2024.09.25.614955. Kok RNU, Spoelstra WK, Betjes MA, van Zon JS, Tans SJ (2025) Label-free cell imaging and tracking in 3D organoids. Cell Rep Phys Sci 6:102522. (PMID: 10.1016/j.xcrp.2025.102522) Konen J, Summerbell E, Dwivedi B, Galior K, Hou Y, Rusnak L, Chen A, Saltz J, Zhou W, Boise LH et al (2017) Image-guided genomics of phenotypically heterogeneous populations reveals vascular signalling during symbiotic collective cancer invasion. Nat Commun 8:1–15. (PMID: 10.1038/ncomms15078) Korsunsky I, Millard N, Fan J, Slowikowski K, Zhang F, Wei K, Baglaenko Y, Brenner M, Loh P-R, Raychaudhuri S (2019) Fast, sensitive and accurate integration of single-cell data with Harmony. Nat Methods 16:1289–1296. (PMID: 10.1038/s41592-019-0619-0317408196884693) Köster J, Rahmann S (2012) Snakemake-a scalable bioinformatics workflow engine. Bioinformatics 28:2520–2522. (PMID: 10.1093/bioinformatics/bts48022908215) Kraus O, Comitani F, Urbanik J, Kenyon-Dean K, Arumugam L, Saberian S, Wognum C, Celik S, Haque IS (2025) RxRx3-core: benchmarking drug-target interactions in high-content microscopy. Preprint at https://doi.org/10.48550/arXiv.2503.20158. Kraus O, Kenyon-Dean K, Saberian S, Fallah M, McLean P, Leung J, Sharma V, Khan A, Balakrishnan J, Celik S, et al (2024) Masked autoencoders for microscopy are scalable learners of cellular biology. In 2024 IEEE/CVF Conference on Computer Vision and Pattern Recognition (CVPR). IEEE, pp 11757–11768. Kraus OZ, Ba JL, Frey BJ (2016) Classifying and segmenting microscopy images with deep multiple instance learning. Bioinformatics 32:i52–i59. (PMID: 10.1093/bioinformatics/btw252273076444908336) Krentzel D, Elphick M, Domart M-C, Peddie CJ, Laine RF, Shand C, Henriques R, Collinson LM, Jones ML (2025) CLEM-Reg: an automated point cloud-based registration algorithm for volume correlative light and electron microscopy. Nat Methods 22:1923–1934. Krispin S, van Zuiden W, Danino YM, Molitor L, Rudberg N, Bar C, Coyne A, Meimoun T, Waldron FM, Gregory JM et al (2025) Organellomics: AI-driven deep organellar phenotyping reveals novel ALS mechanisms in human neurons. Preprint at bioRxiv https://doi.org/10.1101/2024.01.31.572110. Krizhevsky A et al (2017) ImageNet classification with deep convolutional neural networks. Commun ACM 60:84–90. Kudo T, Meireles AM, Moncada R, Chen Y, Wu P, Gould J, Hu X, Kornfeld O, Jesudason R, Foo C et al (2024) Multiplexed, image-based pooled screens in primary cells and tissues with PerturbView. Nat Biotechnol 43:1091–1100. Labitigan RLD, Sanborn AL, Hao CV, Chan CK, Belliveau NM, Brown EM, Mehrotra M, Theriot JA (2024) Mapping variation in the morphological landscape of human cells with optical pooled CRISPRi screening. eLife 13:1–9. Lafarge MW, Caicedo JC, Carpenter AE, Pluim JPW, Singh S, Veta M (2019) Capturing single-cell phenotypic variation via unsupervised representation learning. Proc Mach Learn Res 103:315–325. (PMID: 358746009307238) Lamiable A, Champetier T, Leonardi F, Cohen E, Sommer P, Hardy D, Argy N, Massougbodji A, Del Nery E, Cottrell G et al (2023) Revealing invisible cell phenotypes with conditional generative modeling. Nat Commun 14:6386. (PMID: 10.1038/s41467-023-42124-63782145010567685) Le T, Lundberg E (2024) High-resolution in silico painting with generative models. Preprint at bioRxiv https://doi.org/10.1101/2024.05.31.596710. Lefebvre AEYT, Sturm G, Lin T-Y, Stoops E, López MP, Kaufmann-Malaga B, Hake K (2025) Nellie: automated organelle segmentation, tracking and hierarchical feature extraction in 2D/3D live-cell microscopy. Nat Methods 22:751–763. (PMID: 10.1038/s41592-025-02612-74001632911978511) Leigh R, Gault D, Linkert M, Burel J-M, Moore J, Besson S & Swedlow JR (2017) OME Files - An open source reference library for the OME-XML metadata model and the OME-TIFF file format. bioRxiv: 088740. Leys C, Klein O, Dominicy Y, Ley C (2018) Detecting multivariate outliers: Use a robust variant of the Mahalanobis distance. J Exp Soc Psychol 74:150–156. (PMID: 10.1016/j.jesp.2017.09.011) Li B, Zhang B, Zhang C, Zhou M, Huang W, Wang S, Wang Q, Li M, Zhang Y, Song Q (2025) PhenoProfiler: advancing phenotypic learning for image-based drug discovery. Nat Commun 17:793. Li C, Rai MR, Ghashghaei HT, Greenbaum A (2022) Illumination angle correction during image acquisition in light-sheet fluorescence microscopy using deep learning. Biomed Opt Express 13:888–901. (PMID: 10.1364/BOE.447392352841568884226) Li X, Wang K, Lyu Y, Pan H, Zhang J, Stambolian D, Susztak K, Reilly MP, Hu G, Li M (2020) Deep learning enables accurate clustering with batch effect removal in single-cell RNA-seq analysis. Nat Commun 11:1–14. Lim J, Park C, Kim M, Kim H, Kim J, Lee D-S (2024) Advances in single-cell omics and multiomics for high-resolution molecular profiling. Exp Mol Med 56:515–526. (PMID: 10.1038/s12276-024-01186-23844359410984936) Lin A, Lu AX (2022) Incorporating knowledge of plates in batch normalization improves generalization of deep learning for microscopy images. Preprint at bioRxiv https://doi.org/10.1101/2022.10.14.512286. Lippincott MJ, Tomkinson J, Bilem I, Suzuki M, Nakde A, Endou T, Mathien S, Lavoie-Perusse F, Basualto-Alarcón C, Way GP (2025a) High-content live-cell time-lapse imaging predicts cells about to die via apoptosis. Preprint at bioRxiv https://doi.org/10.1101/2025.10.23.684203. Lippincott MJ, Tomkinson J, Bunten D, Mohammadi M, Kastl J, Knop J, Schwandner R, Huang J, Ongo G, Robichaud N et al (2025b) A morphology and secretome map of pyroptosis. Mol Biol Cell 36:ar63. (PMID: 10.1091/mbc.E25-03-01194020283212206506) Liu B, Zhu Y, Yang Z, Yan HHN, Leung SY, Shi J (2024a) Deep learning-based 3D single-cell imaging analysis pipeline enables quantification of cell-cell interaction dynamics in the tumor microenvironment. Cancer Res 84:517–526. (PMID: 10.1158/0008-5472.CAN-23-110038085180) Liu G, Seal S, Arevalo J, Liang Z, Carpenter AE, Jiang M, Singh S (2024b) Learning molecular representation in a cell. Preprint at https://doi.org/10.48550/arXiv.2406.12056. Liu Y, Huang K, Chen W (2024c) Resolving cellular dynamics using single-cell temporal transcriptomics. Curr Opin Biotechnol 85:103060. (PMID: 10.1016/j.copbio.2023.10306038194753) Liu Z, Hirata-Miyasaki E, Pradeep S, Rahm JV, Foley C, Chandler T, Ivanov IE, Woosley HO, Lee S-C, Khadka S et al (2025) Robust virtual staining of landmark organelles with Cytoland. Nat Mach Intell 7:901–915. (PMID: 10.1038/s42256-025-01046-2) Ljosa V, Caie PD, Ter Horst R, Sokolnicki KL, Jenkins EL, Daya S, Roberts ME, Jones TR, Singh S, Genovesio A et al (2013) Comparison of methods for image-based profiling of cellular morphological responses to small-molecule treatment. J Biomol Screen 18:1321–1329. Longo L, Lapuschkin S, Seifert C (2024) Explainable artificial intelligence. In: Second World Conference, xAI 2024, Valletta, Malta, Proceedings, Part II. Springer Nature. Loo L-H, Wu LF, Altschuler SJ (2007) Image-based multivariate profiling of drug responses from single cells. Nat Methods 4:445–453. (PMID: 10.1038/nmeth103217401369) Lopez R, Regier J, Cole MB, Jordan MI, Yosef N (2018) Deep generative modeling for single-cell transcriptomics. Nat Methods 15:1053–1058. (PMID: 10.1038/s41592-018-0229-2305048866289068) Lotfollahi M, Klimovskaia Susmelj A, De Donno C, Hetzel L, Ji Y, Ibarra IL, Srivatsan SR, Naghipourfar M, Daza RM, Martin B et al (2023) Predicting cellular responses to complex perturbations in high-throughput screens. Mol Syst Biol 19:e11517. (PMID: 10.15252/msb.2022115173715409110258562) Lotfollahi M, Naghipourfar M, Luecken MD, Khajavi M, Büttner M, Wagenstetter M, Avsec Ž, Gayoso A, Yosef N, Interlandi M et al (2022) Mapping single-cell data to reference atlases by transfer learning. Nat Biotechnol 40:121–130. (PMID: 10.1038/s41587-021-01001-734462589) Lu AX, Kraus OZ, Cooper S, Moses AM (2019) Learning unsupervised feature representations for single cell microscopy images with paired cell inpainting. PLoS Comput Biol 15:e1007348. (PMID: 10.1371/journal.pcbi.1007348314794396743779) Luecken MD, Büttner M, Chaichoompu K, Danese A, Interlandi M, Mueller MF, Strobl DC, Zappia L, Dugas M, Colomé-Tatché M et al (2022) Benchmarking atlas-level data integration in single-cell genomics. Nat Methods 19:41–50. (PMID: 10.1038/s41592-021-01336-834949812) Lukonin I, Zinner M, Liberali P (2021) Organoids in image-based phenotypic chemical screens. Exp Mol Med 53:1495–1502. (PMID: 10.1038/s12276-021-00641-8346639388569209) Luna D, Johnson EC, Dunphy LJ, McQuillen R (2024) DeepPaint: a deep-learning package for cell painting image classification. Preprint at bioRxiv https://doi.org/10.1101/2024.10.08.617198. Lundberg S, Lee S-I (2017) A unified approach to interpreting model predictions. Preprint at https://doi.org/10.48550/arXiv.1705.07874. Lundholt BK, Scudder KM, Pagliaro AL (2003) Technical notes: a simple technique for reducing edge effect in cell-based assays. SLAS Discov 8:566–570. (PMID: 10.1177/1087057103256465) Luo J, Fu J, Lu Z, Tu J (2024) Deep learning in integrating spatial transcriptomics with other modalities. Brief Bioinform 26:bbae719. Ma J, He Y, Li F, Han L, You C, Wang B (2024) Segment anything in medical images. Nat Commun 15:1–9. Ma J, Hu C, Zhou P, Jin F, Wang X, Huang H (2023) Review of image augmentation used in deep learning-based material microscopic image segmentation. Appl Sci 13:6478. (PMID: 10.3390/app13116478) Madan A, Saini R, Dhiman N, Juan S-H, Satapathy MK (2025) Organoids as next-generation models for tumor heterogeneity, personalized therapy, and cancer research: advancements, applications, and future directions. Organoids 4:23. (PMID: 10.3390/organoids4040023) Mahmud BU, Hong GY, Mamun AA, Ping EP, Wu Q (2023) Deep learning-based segmentation of 3D volumetric image and microstructural analysis. Sensors 23:2640. (PMID: 10.3390/s230526403690484510007404) Marks M, Israel U, Dilip R, Li Q, Yu C, Laubscher E, Iqbal A, Pradhan E, Ates A, Abt M et al. (2025) CellSAM: a foundation model for cell segmentation. Nat Methods 22:2585–2593. Mattiazzi Usaj M, Yeung CHL, Friesen H, Boone C, Andrews BJ (2021) Single-cell image analysis to explore cell-to-cell heterogeneity in isogenic populations. Cell Syst 12:608–621. (PMID: 10.1016/j.cels.2021.05.010341391689112900) Maška M, Ulman V, Delgado-Rodriguez P, Gómez-de-Mariscal E, Nečasová T, Guerrero Peña FA, Ren TI, Meyerowitz EM, Scherr T, Löffler K et al (2023) The cell tracking challenge: 10 years of objective benchmarking. Nat Methods 20:1010–1020. (PMID: 10.1038/s41592-023-01879-y3720253710333123) Meng G, Zhou R, Liu L, Liang P, Liu F, Chen D, Niemier M, Hu XS (2024) Efficient approximation of Earth Mover’s Distance based on nearest neighbor search. Preprint at https://doi.org/10.48550/arXiv.2401.07378. Michael Ando D, McLean CY, Berndl M (2017) Improving phenotypic measurements in high-content imaging screens. Preprint at bioRxiv https://doi.org/10.1101/161422. Milacic M, Beavers D, Conley P, Gong C, Gillespie M, Griss J, Haw R, Jassal B, Matthews L, May B et al (2023) The Reactome pathway knowledgebase 2024. Nucleic Acids Res 52:D672–D678. (PMID: 10.1093/nar/gkad1025) Moore J, Basurto-Lozada D, Besson S, Bogovic J, Bragantini J, Brown EM, Burel J-M, Casas Moreno X, de Medeiros G, Diel EE et al (2023) OME-Zarr: a cloud-optimized bioimaging file format with international community support. Histochem Cell Biol 160:223–251. Moraes-Lacerda T, Rodrigues-Da-Silva M, Singh S, De Jesus MB (2025) Image-based profiling in live cells using live cell painting. Bio Protoc 15:e5464. (PMID: 10.21769/BioProtoc.54644108044712514141) Morelli FM, Kim V, Hecker F, Geibel S, Marín Zapata PA (2025) uniDINO: Assay-independent feature extraction for fluorescence microscopy images. Comput Struct Biotechnol J 27:928–936. (PMID: 10.1016/j.csbj.2025.02.0204012380111930362) Moshkov N, Becker T, Yang K, Horvath P, Dancik V, Wagner BK, Clemons PA, Singh S, Carpenter AE, Caicedo JC (2023) Predicting compound activity from phenotypic profiles and chemical structures. Nat Commun 14:1967. (PMID: 10.1038/s41467-023-37570-13703120810082762) Moshkov N, Bornholdt M, Benoit S, Smith M, McQuin C, Goodman A, Senft RA, Han Y, Babadi M, Horvath P et al (2024) Learning representations for image-based profiling of perturbations. Nature Communications 15:1–17. (PMID: 10.1038/s41467-024-45999-1) Mousavikhamene Z, Sykora DJ, Mrksich M, Bagheri N (2021) Morphological features of single cells enable accurate automated classification of cancer from non-cancer cell lines. Sci Rep 11:24375. (PMID: 10.1038/s41598-021-03813-8349341498692621) Murthy RS, Stassen SV, Siu DMD, Lo MCK, Yip GGK, Tsia KK (2025) Generalizable morphological profiling of cells by interpretable unsupervised learning. Nat Commun 16:11465. Nassiri I, McCall MN (2018) Systematic exploration of cell morphological phenotypes associated with a transcriptomic query. Nucleic Acids Res 46:e116. (PMID: 10.1093/nar/gky626300110386212779) Navidi Z, Ma J, Miglietta EA, Liu L, Carpenter AE, Cimini BA, Haibe-Kains B, Wang B (2024) MorphoDiff: cellular morphology painting with diffusion models. Preprint at bioRxiv https://doi.org/10.1101/2024.12.19.629451. Neumann B, Walter T, Hériché JK, Bulkescher J, Erfle H, Conrad C, Rogers P, Poser I, Held M, Liebel U et al (2010) Phenotypic profiling of the human genome by time-lapse microscopy reveals cell division genes. Nature 464:721–727. Nyffeler J, Haggard DE, Willis C, Setzer RW, Judson R, Paul-Friedman K, Everett LJ, Harrill JA (2021) Comparison of approaches for determining bioactivity hits from high-dimensional profiling data. SLAS Discov 26:292–308. (PMID: 10.1177/247255522095024532862757) O’Connor OM, Dunlop MJ (2025) Cell-TRACTR: A transformer-based model for end-to-end segmentation and tracking of cells. PLoS Comput Biol 21:e1013071. (PMID: 10.1371/journal.pcbi.10130714040863112101859) Okoro G, Wityk P, Nelappana MB, Jackiewicz KA, Kucharczyk VZ, Tigranyan A, Applegate CC, Dobrucki IT, Dobrucki LW (2025) A graph-theoretic framework for quantitative analysis of angiogenic networks. BioData Min 18:69. (PMID: 10.1186/s13040-025-00478-14103957912492523) Omta WA, van Heesbeen RG, Pagliero RJ, van der Velden LM, Lelieveld D, Nellen M, Kramer M, Yeong M, Saeidi AM, Medema RH et al (2016) HC StratoMineR: a web-based tool for the rapid analysis of high-content datasets. Assay Drug Dev Technol 14:439–452. (PMID: 10.1089/adt.2016.72627636821) Ong HT, Karatas E, Poquillon T, Grenci G, Furlan A, Dilasser F, Mohamad Raffi SB, Blanc D, Drimaracci E, Mikec D et al (2025) Digitalized organoids: integrated pipeline for high-speed 3D analysis of organoid structures using multilevel segmentation and cellular topology. Nat Methods 22:1343–1354. O’Shea K, Nash R (2015) An introduction to convolutional neural networks. Preprint at https://doi.org/10.48550/arXiv.1511.08458. Ounkomol C, Seshamani S, Maleckar MM, Collman F, Johnson GR (2018) Label-free prediction of three-dimensional fluorescence images from transmitted-light microscopy. Nat Methods 15:917–920. (PMID: 10.1038/s41592-018-0111-2302246726212323) Padovani F, Mairhörmann B, Falter-Braun P, Lengefeld J, Schmoller KM (2022) Segmentation, tracking and cell cycle analysis of live-cell imaging data with Cell-ACDC. BMC Biol 20:174. (PMID: 10.1186/s12915-022-01372-6359320439356409) Pahl A, Schölermann B, Lampe P, Rusch M, Dow M, Hedberg C, Nelson A, Sievers S, Waldmann H, Ziegler S (2023) Morphological subprofile analysis for bioactivity annotation of small molecules. Cell Chem Biol 30:839–853.e7. (PMID: 10.1016/j.chembiol.2023.06.00337385259) Palma A, Theis FJ, Lotfollahi M (2025) Predicting cell morphological responses to perturbations using generative modeling. Nat Commun 16:505. (PMID: 10.1038/s41467-024-55707-83977967511711326) Pawlowski N, Caicedo JC, Singh S, Carpenter AE, Storkey A (2016) Automating morphological profiling with generic deep convolutional networks. Preprint at bioRxiv https://doi.org/10.1101/085118. Pearson YE, Kremb S, Butterfoss GL, Xie X, Fahs H, Gunsalus KC (2022) A statistical framework for high-content phenotypic profiling using cellular feature distributions. Commun Biol 5:1409. (PMID: 10.1038/s42003-022-04343-3365502899780213) Perera S, Navard P & Yilmaz A (2024) SegFormer3D: an Efficient Transformer for 3D Medical Image Segmentation. In 2024 IEEE/CVF Conference on Computer Vision and Pattern Recognition Workshops (CVPRW). IEEE, pp 4981–4988. Pernice WM, Doron M, Quach A, Pratapa A, Kenjeyev S, De Veaux N, Hirano M & Caicedo JC (2023) Out of distribution generalization via interventional style transfer in single-cell microscopy. In 2023 IEEE/CVF Conference on Computer Vision and Pattern Recognition Workshops (CVPRW). IEEE, pp 4326–4335. Pfaendler R, Hanimann J, Lee S, Snijder B (2023) Self-supervised vision transformers accurately decode cellular state heterogeneity. Preprint at bioRxiv https://doi.org/10.1101/2023.01.16.524226. Pham C, Caicedo JC, Plummer BA (2025) ChA-MAEViT: unifying channel-aware masked autoencoders and multi-channel vision transformers for improved cross-channel learning. Preprint at https://doi.org/10.48550/arXiv.2503.19331. Pratapa A, Doron M, Caicedo JC (2021) Image-based cell phenotyping with deep learning. Curr Opin Chem Biol 65:9–17. (PMID: 10.1016/j.cbpa.2021.04.00134023800) Pylvänäinen JW, Grobe H, Jacquemet G (2025) Practical considerations for data exploration in quantitative cell biology. J Cell Sci 138:jcs263801. Qiu M, Zhou B, Lo F, Cook S, Chyba J, Quackenbush D, Matzen J, Li Z, Mak PA, Chen K et al (2020) A cell-level quality control workflow for high-throughput image analysis. BMC Bioinformatics 21:280. (PMID: 10.1186/s12859-020-03603-5326159177333376) Rai MR, Li C, Greenbaum A (2022) Quantitative analysis of illumination and detection corrections in adaptive light sheet fluorescence microscopy. Biomed Opt Express 13:2960–2974. (PMID: 10.1364/BOE.454561357743329203118) Rajaram S, Pavie B, Wu LF, Altschuler SJ (2012) PhenoRipper: software for rapidly profiling microscopy images. Nat Methods 9:635–637. (PMID: 10.1038/nmeth.2097227437643842428) Ramezani M, Weisbart E, Bauman J, Singh A, Yong J, Lozada M, Way GP, Kavari SL, Diaz C, Leardini E et al (2025) A genome-wide atlas of human cell morphology. Nat Methods 22:621–633. (PMID: 10.1038/s41592-024-02537-73987086211903339) Ramm S, Vary R, Gulati T, Luu J, Cowley KJ, Janes MS, Radio N, Simpson KJ (2022) High-throughput live and fixed cell imaging method to screen Matrigel-embedded organoids. Organoids 2:1–19. (PMID: 10.3390/organoids2010001) Razdaibiedina A, Brechalov A, Friesen H, Mattiazzi Usaj M, Masinas MPD, Garadi Suresh H, Wang K, Boone C, Ba J, Andrews B (2024) PIFiA: self-supervised approach for protein functional annotation from single-cell imaging data. Mol Syst Biol 20:521–548. (PMID: 10.1038/s44320-024-00029-63847230511066028) Reisen F, Zhang X, Gabriel D, Selzer P (2013) Benchmarking of multivariate similarity measures for high-content screening fingerprints in phenotypic drug discovery. J Biomol Screen 18:1284–1297. (PMID: 10.1177/108705711350139024045583) Rezvani A, Bigverdi M, Rohban MH (2022) Image-based cell profiling enhancement via data cleaning methods. PLoS ONE 17:e0267280. (PMID: 10.1371/journal.pone.0267280355075599067647) Riccardo B, Andrea C, Stefano G, Giovanna N, Eleonora V (2021) The gene mover’s distance: single-cell similarity via optimal transport. Preprint at https://doi.org/10.48550/arXiv.2102.01218. Riley P (2019) Three pitfalls to avoid in machine learning. Nature 572:27–29. (PMID: 10.1038/d41586-019-02307-y31363197) Ringers C, Holmberg D, Flobak Å, Georgiev P, Jarvius M, Johansson M, Larsson A, Rosen D, Seashore-Ludlow B, Visnes T et al (2025) High-content morphological profiling by Cell Painting in 3D spheroids. Preprint at bioRxiv https://doi.org/10.1101/2025.02.05.636642. Risso D, Ngai J, Speed TP, Dudoit S (2014) Normalization of RNA-seq data using factor analysis of control genes or samples. Nat Biotechnol 32:896–902. (PMID: 10.1038/nbt.2931251508364404308) Rohban MH, Abbasi HS, Singh S, Carpenter AE (2019) Capturing single-cell heterogeneity via data fusion improves image-based profiling. Nat Commun 10:2082. (PMID: 10.1038/s41467-019-10154-8310649856504923) Ronneberger O, Fischer P, Brox T (2015) U-Net: convolutional networks for biomedical image segmentation. Med Image Comput Comput Assist Interv 2015:234–241. Rotem O, Schwartz T, Maor R, Tauber Y, Shapiro MT, Meseguer M, Gilboa D, Seidman DS, Zaritsky A (2024) Visual interpretability of image-based classification models by generative latent space disentanglement applied to in vitro fertilization. Nat Commun 15:7390. (PMID: 10.1038/s41467-024-51136-93919172011349992) Rotem O, Zaritsky A (2024) Visual interpretability of bioimaging deep learning models. Nat Methods 21:1394–1397. (PMID: 10.1038/s41592-024-02322-639122948) Rubner Y, Tomasi C, Guibas LJ (2000) The earth mover’s distance as a metric for image retrieval. Int J Comput Vis 40:99–121. Rubner Y, Tomasi C, Guibas LJ (2002) A metric for distributions with applications to image databases. In: Sixth international conference on computer vision (IEEE Cat. No.98CH36271). Narosa Publishing House. Sanchez-Fernandez A, Rumetshofer E, Hochreiter S, Klambauer G (2023) CLOOME: contrastive learning unlocks bioimaging databases for queries with chemical structures. Nat Commun 14:7339. (PMID: 10.1038/s41467-023-42328-w3795720710643690) Scheeder C, Heigwer F, Boutros M (2018) Machine learning and image-based profiling in drug discovery. Curr Opin Syst Biol 10:43. (PMID: 10.1016/j.coisb.2018.05.004301594066109111) Schiff L, Migliori B, Chen Y, Carter D, Bonilla C, Hall J, Fan M, Tam E, Ahadi S, Fischbacher B et al (2022) Integrating deep learning and unbiased automated high-content screening to identify complex disease signatures in human fibroblasts. Nat Commun 13:1–13. (PMID: 10.1038/s41467-022-28423-4) Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, Preibisch S, Rueden C, Saalfeld S, Schmid B et al (2012) Fiji: an open-source platform for biological-image analysis. Nat Methods 9:676–682. (PMID: 10.1038/nmeth.2019227437723855844) Schmidt U, Weigert M, Broaddus C, Myers G (2018) Cell detection with star-convex polygons. In Medical Image Computing and Computer Assisted Intervention – MICCAI 2018. Cham: Springer International Publishing, pp 265–273. Schneider L, Laiouar-Pedari S, Kuntz S, Krieghoff-Henning E, Hekler A, Kather JN, Gaiser T, Fröhling S, Brinker TJ (2022) Integration of deep learning-based image analysis and genomic data in cancer pathology: a systematic review. Eur J Cancer 160:80–91. Schneidewind T, Kapoor S, Garivet G, Karageorgis G, Narayan R, Vendrell-Navarro G, Antonchick AP, Ziegler S, Waldmann H (2019) The pseudo natural product Myokinasib is a myosin light chain kinase 1 inhibitor with unprecedented chemotype. Cell Chem Biol 26:512–523.e5. (PMID: 10.1016/j.chembiol.2018.11.01430686759) Schober P, Boer C, Schwarte LA (2018) Correlation coefficients: Appropriate use and interpretation. Anesth Analg 126:1763–1768. (PMID: 10.1213/ANE.000000000000286429481436) Schwartz MS, Moen E, Miller G, Dougherty T, Borba E, Ding R, Graf W, Pao E, Van Valen D (2019) Caliban: accurate cell tracking and lineage construction in live-cell imaging experiments with deep learning. Preprint at bioRxiv https://doi.org/10.1101/803205. Seal S, Carreras-Puigvert J, Singh S, Carpenter AE, Spjuth O, Bender A (2024a) From pixels to phenotypes: integrating image-based profiling with cell health data as BioMorph features improves interpretability. Mol Biol Cell 35:mr2. Seal S, Carreras-Puigvert J, Trapotsi M-A, Yang H, Spjuth O, Bender A (2022) Integrating cell morphology with gene expression and chemical structure to aid mitochondrial toxicity detection. Commun Biol 5:858. (PMID: 10.1038/s42003-022-03763-5359994579399120) Seal S, Dee W, Shah A, Zhang A, Titterton K, Cabrera ÁA, Boiko D, Beatson A, Puigvert JC, Singh S et al (2025) Small molecule bioactivity benchmarks are often well-predicted by counting cells. Preprint at bioRxiv https://doi.org/10.1101/2025.04.27.650853. Seal S, Trapotsi M-A, Spjuth O, Singh S, Carreras-Puigvert J, Greene N, Bender A, Carpenter AE (2024b) Cell Painting: a decade of discovery and innovation in cellular imaging. Nat Methods 22:254–268. (PMID: 10.1038/s41592-024-02528-83963916811810604) Serrano E, Chandrasekaran SN, Bunten D, Brewer KI, Tomkinson J, Kern R, Bornholdt M, Fleming SJ, Pei R, Arevalo J et al (2025) Reproducible image-based profiling with Pycytominer. Nat Methods 22:677–680. (PMID: 10.1038/s41592-025-02611-84003299512121495) Sexton JZ, Fursmidt R, O’Meara MJ, Omta W, Rao A, Egan DA, Haney SA (2023) Machine learning and assay development for image-based phenotypic profiling of drug treatments. In: Assay guidance manual [Internet]. Eli Lilly & Company and the National Center for Advancing Translational Sciences. Sharma O, Gudoityte G, Minozada R, Kallioniemi OP, Turkki R, Paavolainen L, Seashore-Ludlow B (2025) Evaluating feature extraction in ovarian cancer cell line co-cultures using deep neural networks. Commun Biol 8:303. (PMID: 10.1038/s42003-025-07766-w4000076411862010) Shave S, Dawson JC, Athar AM, Nguyen CQ, Kasprowicz R, Carragher NO (2023) Phenonaut: multiomics data integration for phenotypic space exploration. Bioinformatics 39:btad143. Shpigler A, Kolet N, Golan S, Weisbart E, Zaritsky A (2025) Anomaly detection for high-content image-based phenotypic cell profiling. Cell Syst 16:101429. Singh S, Bray M-A, Jones TR, Carpenter AE (2014) Pipeline for illumination correction of images for high-throughput microscopy. J Microsc 256:231–236. (PMID: 10.1111/jmi.12178252282404359755) Sinning K, Hochrein SM, Gubert GF, Vaeth M (2025) Metabolic profiling of activated T lymphocytes using single-cell energetic metabolism by profiling translation inhibition (SCENITH). Methods Mol Biol 2904:259–271. (PMID: 10.1007/978-1-0716-4414-0_1840220239) Sivagurunathan S, Byrne P, Muñoz AF, Arevalo J, Carpenter AE, Singh S, Kost-Alimova M, Cimini BA (2025) Alternate dyes for image-based profiling assays. SLAS Discov 36:100268. Sivanandan S, Leitmann B, Lubeck E, Sultan MM, Stanitsas P, Ranu N, Ewer A, Mancuso JE, Phillips ZF, Kim A et al. (2025) A pooled Cell Painting CRISPR screening platform enables de novo inference of gene function by self-supervised deep learning. Nat Commun 17:77. Škuta C, Müller T, Voršilák M, Popr M, Epp T, Skopelitou KE, Rossella F, Stechmann B, Gribbon P, Bartůněk P (2025) ECBD: European chemical biology database. Nucleic Acids Res 53:D1383–D1392. (PMID: 10.1093/nar/gkae9043944106511701612) Steiner A, Kolesnikov A, Zhai X, Wightman R, Uszkoreit J, Beyer L (2021) How to train your ViT? Data, augmentation, and regularization in vision transformers. Preprint at https://doi.org/10.48550/arXiv.2106.10270. Stirling DR, Swain-Bowden MJ, Lucas AM, Carpenter AE, Cimini BA, Goodman A (2021) CellProfiler 4: improvements in speed, utility and usability. BMC Bioinformatics 22:1–11. (PMID: 10.1186/s12859-021-04344-9) Stossi F, Singh PK, Marini M, Safari K, Szafran AT, Rivera TA, Candler CD, Mancini MG, Mosa EA, Bolt MJ et al (2024) SPACe: an open-source, single-cell analysis of Cell Painting data. Nat Commun 15:10170. Stossi F, Singh PK, Mistry RM, Johnson HL, Dandekar RD, Mancini MG, Szafran AT, Rao AU, Mancini MA (2022) Quality control for single cell imaging analytics using endocrine disruptor-induced changes in estrogen receptor expression. Environ Health Perspect 130:27008. (PMID: 10.1289/EHP9297351673268846386) Stossi F, Singh PK, Safari K, Marini M, Labate D, Mancini MA (2023) High throughput microscopy and single cell phenotypic image-based analysis in toxicology and drug discovery. Biochem Pharmacol 216:115770. (PMID: 10.1016/j.bcp.2023.11577037660829) Stoudt S, Vásquez VN, Martinez CC (2021) Principles for data analysis workflows. PLoS Comput Biol 17:e1008770. (PMID: 10.1371/journal.pcbi.1008770337352087971542) Stringer C, Wang T, Michaelos M, Pachitariu M (2020) Cellpose: a generalist algorithm for cellular segmentation. Nat Methods 18:100–106. (PMID: 10.1038/s41592-020-01018-x33318659) Stuart T, Butler A, Hoffman P, Hafemeister C, Papalexi E, Mauck WM 3rd, Hao Y, Stoeckius M, Smibert P, Satija R (2019) Comprehensive integration of single-cell data. Cell 177:1888–1902.e21. (PMID: 10.1016/j.cell.2019.05.031311781186687398) Subramanian A, Alperovich M, Yang Y, Li B (2022) Biology-inspired data-driven quality control for scientific discovery in single-cell transcriptomics. Genome Biol 23:267. (PMID: 10.1186/s13059-022-02820-w365755239793662) Sullivan DP, Winsnes CF, Åkesson L, Hjelmare M, Wiking M, Schutten R, Campbell L, Leifsson H, Rhodes S, Nordgren A et al (2018) Deep learning is combined with massive-scale citizen science to improve large-scale image classification. Nat Biotechnol 36:820–828. (PMID: 10.1038/nbt.422530125267) Sypetkowski M, Rezanejad M, Saberian S, Kraus O, Urbanik J, Taylor J, Mabey B, Victors M, Yosinski J, Sereshkeh AR et al (2023) RxRx1: a dataset for evaluating experimental batch correction methods. In: 2023 IEEE/CVF conference on computer vision and pattern recognition workshops (CVPRW). IEEE, pp 4285–4294. Szklarczyk D, Kirsch R, Koutrouli M, Nastou K, Mehryary F, Hachilif R, Gable AL, Fang T, Doncheva NT, Pyysalo S et al (2022) The STRING database in 2023: protein–protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res 51:D638–D646. (PMID: 10.1093/nar/gkac1000) Tan M, Le QV (2019) EfficientNet: rethinking model scaling for convolutional Neural Networks. ICML abs/1905.11946:6105–6114. Tang Q, Ratnayake R, Seabra G, Jiang Z, Fang R, Cui L, Ding Y, Kahveci T, Bian J, Li C et al (2024) Morphological profiling for drug discovery in the era of deep learning. Brief Bioinform 25:bbae284. Tanner A (2017) Helpful hints to manage edge effect of cultured cells for high throughput screening. SelectScience. Tegtmeyer M, Liyanage D, Han Y, Hebert KB, Pei R, Way GP, Ryder PV, Hawes D, Tromans-Coia C, Cimini BA et al (2025) Combining phenomics with transcriptomics reveals cell-type-specific morphological and molecular signatures of the 22q11.2 deletion. Nat Commun 16:6332. Teschendorff AE (2019) Avoiding common pitfalls in machine learning omic data science. Nat Mater 18:422–427. (PMID: 10.1038/s41563-018-0241-z30478452) Thul PJ, Åkesson L, Wiking M, Mahdessian D, Geladaki A, Blal HA, Alm T, Asplund A, Björk L, Breckels LM et al (2017) A subcellular map of the human proteome. Science 356:eaal3321. Tian G, Harrison PJ, Sreenivasan AP, Carreras-Puigvert J, Spjuth O (2023) Combining molecular and cell painting image data for mechanism of action prediction. Artif Intell Life Sci 3:100060. Tian S, Wang C, Wang B (2019) Incorporating pathway information into feature selection towards better performed gene signatures. Biomed Res Int 2019:2497509. (PMID: 10.1155/2019/2497509310735226470448) Tomkinson J, Bunten D, Way GP (2025) Stellar quality control for single-cell image-based profiling with coSMicQC. Preprint at bioRxiv https://doi.org/10.1101/2025.10.14.682427. Tomkinson J, Kern R, Mattson C, Way GP (2024) Toward generalizable phenotype prediction from single-cell morphology representations. BMC Methods 1:17. Tonks S, Hsu C-Y, Hood S, Musso R, Hopely C, Titus S, Krull A, Doan M, Styles I (2023) Evaluating virtual staining for high-throughput screening. In: 2023 IEEE 20th international symposium on biomedical imaging (ISBI). IEEE, pp 1–5. Tonks S, Nguyen C, Hood S, Musso R, Hopely C, Titus S, Doan M, Styles I & Krull A (2025) Can virtual staining for high-throughput screening generalize? In Lecture Notes in Computer Science Cham: Springer Nature Switzerland, pp 34–50. Tran HTN, Ang KS, Chevrier M, Zhang X, Lee NYS, Goh M, Chen J (2020) A benchmark of batch-effect correction methods for single-cell RNA sequencing data. Genome Biol 21:12. (PMID: 10.1186/s13059-019-1850-9319484816964114) Travers JG, Tomkinson J, Rubino M, Delaunay M, Bristow MR, Way GP, McKinsey TA (2025) Cell painting and machine learning distinguish fibroblasts from nonfailing and failing human hearts. Circulation 151:1207–1210. van Dijk R, Arevalo J, Babadi M, Carpenter AE, Singh S (2024) Capturing cell heterogeneity in representations of cell populations for image-based profiling using contrastive learning. PLoS Comput Biol 20:e1012547. Vaswani A, Shazeer N, Parmar N, Uszkoreit J, Jones L, Gomez AN, Kaiser Ł & Polosukhin I (2017) Attention is all you need. In Proceedings of the 31st International Conference on Neural Information Processing Systems. Red Hook, NY, USA: Curran Associates Inc., pp 6000–6010. Viana MP, Chen J, Knijnenburg TA, Vasan R, Yan C, Arakaki JE, Bailey M, Berry B, Borensztejn A, Brown EM et al (2023) Integrated intracellular organization and its variations in human iPS cells. Nature 613:345–354. (PMID: 10.1038/s41586-022-05563-7365999839834050) Vicar T, Balvan J, Jaros J, Jug F, Kolar R, Masarik M, Gumulec J (2019) Cell segmentation methods for label-free contrast microscopy: review and comprehensive comparison. BMC Bioinformatics 20:1–25. (PMID: 10.1186/s12859-019-2880-8) Victors M, Earnshaw B, Khaliullin R, Borgeson B, McLean P, Lazar N, Skelly K-R (2025) Systems and methods for evaluating query perturbations. US Patent 20250078976, 29 March 2025. Virshup I, Bredikhin D, Heumos L, Palla G, Sturm G, Gayoso A, Kats I, Koutrouli M, Scverse Community, Berger B et al (2023) The scverse project provides a computational ecosystem for single-cell omics data analysis. Nat Biotechnol 41:604–606. (PMID: 10.1038/s41587-023-01733-837037904) Virshup I, Rybakov S, Theis FJ, Angerer P, Wolf FA (2021) anndata: annotated data. Preprint at bioRxiv https://doi.org/10.1101/2021.12.16.473007. Vulliard L, Hancock J, Kamnev A, Fell CW, da Silva JF, Loizou JI, Nagy V, Dupré L, Menche J (2022) BioProfiling.jl: profiling biological perturbations with high-content imaging in single cells and heterogeneous populations. Bioinformatics 38:1692–1699. Wagner J, Warden H, Khamseh A, Beentjes SV (2025) scmorph: a Python package for analysing single-cell morphological profiles. J Open Source Softw 10:8324. Walton RT, Singh A, Blainey PC (2022) Pooled genetic screens with image-based profiling. Mol Syst Biol 18:e10768. Wang A, Zhang Q, Han Y, Megason S, Hormoz S, Mosaliganti KR, Lam JCK, Li VOK (2022) A novel deep learning-based 3D cell segmentation framework for future image-based disease detection. Sci Rep 12:342. (PMID: 10.1038/s41598-021-04048-3350134438748745) Wang J, Wang X, Zhang P, Xie S, Fu S, Li Y, Han H (2021) Correction of uneven illumination in color microscopic image based on fully convolutional network. Opt Express 29:28503–28520. (PMID: 10.1364/OE.43306434614979) Wang K, Yang Y, Wu F, Song B, Wang X, Wang T (2023a) Comparative analysis of dimension reduction methods for cytometry by time-of-flight data. Nat Commun 14:1836. (PMID: 10.1038/s41467-023-37478-w3700547210067013) Wang S, Han Q, Qin W, Wang L, Yuan J, Zhao Y, Ren P, Zhang Y, Tang Y, Li R et al (2024a) PhenoScreen: a dual-space contrastive learning framework-based phenotypic screening method by linking chemical perturbations to cellular morphology. Preprint at bioRxiv https://doi.org/10.1101/2024.10.23.619752. Wang S, Liu X, Li Y, Sun X, Li Q, She Y, Xu Y, Huang X, Lin R, Kang D et al (2023b) A deep learning-based stripe self-correction method for stitched microscopic images. Nat Commun 14:5393. (PMID: 10.1038/s41467-023-41165-13766997710480181) Wang T, Johnson TS, Shao W, Lu Z, Helm BR, Zhang J, Huang K (2019) BERMUDA: a novel deep transfer learning method for single-cell RNA sequencing batch correction reveals hidden high-resolution cellular subtypes. Genome Biol 20:1–15. (PMID: 10.1186/s13059-019-1764-6) Wang W, Douglas D, Zhang J, Kumari S, Enuameh MS, Dai Y, Wallace CT, Watkins SC, Shu W, Xing J (2020) Live-cell imaging and analysis reveal cell phenotypic transition dynamics inherently missing in snapshot data. Sci Adv 6:eaba9319. Wang Y, Zhao J, Xu H, Han C, Tao Z, Zhou D, Geng T, Liu D, Ji Z (2024b) A systematic evaluation of computational methods for cell segmentation. Brief Bioinform 25:bbae407. Wang ZJ, Lopez R, Hütter J-C, Kudo T, Yao H, Hanslovsky P, Höckendorf B, Moran R, Richmond D, Regev A (2023c) Multi-ContrastiveVAE disentangles perturbation effects in single cell images from optical pooled screens. Preprint at bioRxiv https://doi.org/10.1101/2023.11.28.569094. Watson ER, Taherian Fard A, Mar JC (2022) Computational methods for single-cell imaging and omics data integration. Front Mol Biosci 8:768106. (PMID: 10.3389/fmolb.2021.768106351118098801747) Way GP, Kost-Alimova M, Shibue T, Harrington WF, Gill S, Piccioni F, Becker T, Shafqat-Abbasi H, Hahn WC, Carpenter AE et al (2021) Predicting cell health phenotypes using image-based morphology profiling. Mol Biol Cell 32:995–1005. (PMID: 10.1091/mbc.E20-12-0784335346418108524) Way GP, Natoli T, Adeboye A, Litichevskiy L, Yang A, Lu X, Caicedo JC, Cimini BA, Karhohs K, Logan DJ et al (2022a) Morphology and gene expression profiling provide complementary information for mapping cell state. Cell Syst 13:911–923.e9. (PMID: 10.1016/j.cels.2022.10.0013639572710246468) Way GP, Sailem H, Shave S, Kasprowicz R, Carragher NO (2023) Evolution and impact of high content imaging. SLAS Discov 28:292–305. (PMID: 10.1016/j.slasd.2023.08.00937666456) Way GP, Spitzer H, Burnham P, Raj A, Theis F, Singh S, Carpenter AE (2022b) Image-based profiling: a powerful and challenging new data type. Pac Symp Biocomput 27:407–411. Weigert M, Schmidt U (2022) Nuclei instance segmentation and classification in histopathology images with Stardist. In: 2022 IEEE international symposium on biomedical imaging challenges (ISBIC). IEEE. Weisbart E, Kumar A, Arevalo J, Carpenter AE, Cimini BA, Singh S (2024) Cell Painting Gallery: an open resource for image-based profiling. Nat Methods 21:1775–1777. (PMID: 10.1038/s41592-024-02399-z3922339711466682) Wieslander H, Gupta A, Bergman E, Hallström E, Harrison PJ (2021) Learning to see colours: biologically relevant virtual staining for adipocyte cell images. PLoS ONE 16:e0258546. (PMID: 10.1371/journal.pone.0258546346532098519425) Wilkinson, Dumontier M, Aalbersberg IJ, Appleton G, Axton M, Baak A, Blomberg N, Boiten JW, da Silva Santos LB, Bourne PE et al (2016) The FAIR Guiding Principles for scientific data management and stewardship. Sci Data 3:160018. Williams E, Moore J, Li SW, Rustici G, Tarkowska A, Chessel A, Leo S, Antal B, Ferguson RK, Sarkans U et al (2017) The image data resource: a bioimage data integration and publication platform. Nat Methods 14:775–781. (PMID: 10.1038/nmeth.4326287756735536224) Wolf FA, Angerer P, Theis FJ (2018) SCANPY: large-scale single-cell gene expression data analysis. Genome Biol 19:15. (PMID: 10.1186/s13059-017-1382-0294095325802054) Wolff C, Neuenschwander M, Beese CJ, Sitani D, Ramos MC, Srovnalova A, Varela MJ, Polishchuk P, Skopelitou KE, Škuta C et al (2025) Morphological profiling data resource enables prediction of chemical compound properties. iScience 28:112445. (PMID: 10.1016/j.isci.2025.1124454038493012084007) Wong DR, Logan DJ, Hariharan S, Stanton R, Clevert D-A, Kiruluta A (2023) Deep representation learning determines drug mechanism of action from cell painting images. Digital Discovery 2:1354–1367. Wratten L, Wilm A, Göke J (2021) Reproducible, scalable, and shareable analysis pipelines with bioinformatics workflow managers. Nat Methods 18:1161–1168. (PMID: 10.1038/s41592-021-01254-934556866) Xing X, Murdoch S, Tang C, Papanastasiou G, Cross-Zamirski J, Guo Y, Xiao X, Schönlieb C-B, Wang Y, Yang G (2024) Can generative AI replace immunofluorescent staining processes? A comparison study of synthetically generated cellpainting images from brightfield. Comput Biol Med 182:109102. (PMID: 10.1016/j.compbiomed.2024.10910239255659) Xun D, Wang R, Zhang X, Wang Y (2024) Microsnoop: a generalist tool for microscopy image representation. Innovation 5:100541. Yan C, Zhang Y, Feng J, Hua H, Ruan Z, Li Z, Li S, Yan C, Li P, Liu J et al (2025) Triple-effect correction for Cell Painting data with contrastive and domain-adversarial learning. Nat Commun 16:6886. (PMID: 10.1038/s41467-025-62193-z4071512212297272) Yan X, Stuurman N, Ribeiro SA, Tanenbaum ME, Horlbeck MA, Liem CR, Jost M, Weissman JS, Vale RD (2021) High-content imaging-based pooled CRISPR screens in mammalian cells. J Cell Biol 220:e202008158. Yang FW, Tomášová L, Guttenberg ZV, Chen K, Madzvamuse A (2020) Investigating optimal time step intervals of imaging for data quality through a novel fully-automated cell tracking approach. J Imaging 6:66. (PMID: 10.3390/jimaging6070066344606598321081) Yang S, Xiao W, Zhang M, Guo S, Zhao J, Shen F (2022) Image data augmentation for deep learning: a survey. Preprint at https://doi.org/10.48550/arXiv.2204.08610. Yao H, Hanslovsky P, Huetter J-C, Hoeckendorf B & Richmond D (2024) Weakly supervised set-consistency learning improves morphological profiling of single-cell images. In 2024 IEEE/CVF Conference on Computer Vision and Pattern Recognition Workshops (CVPRW). pp 6978–6987. Yayon N, Dudai A, Vrieler N, Amsalem O, London M, Soreq H (2018) Intensify3D: normalizing signal intensity in large heterogenic image stacks. Sci Rep 8:4311. (PMID: 10.1038/s41598-018-22489-1295238155844907) Yin L, Siracusa JS, Measel E, Guan X, Edenfield C, Liang S, Yu X (2020) High-content image-based single-cell phenotypic analysis for the testicular toxicity prediction induced by bisphenol A and its analogs bisphenol S, bisphenol AF, and tetrabromobisphenol A in a three-dimensional testicular cell co-culture model. Toxicol Sci 173:313–335. (PMID: 10.1093/toxsci/kfz233317509236986343) Yoon JH, Lee H, Kwon D, Lee D, Lee S, Cho E, Kim J, Kim D (2024) Integrative approach of omics and imaging data to discover new insights for understanding brain diseases. Brain Commun 6:fcae265. (PMID: 10.1093/braincomms/fcae2653916547911334939) Yoshida SR, Maity BK, Chong S (2023) Visualizing protein localizations in fixed cells: caveats and the underlying mechanisms. J Phys Chem B 127:4165–4173. (PMID: 10.1021/acs.jpcb.3c016583716190410201523) Young DW, Bender A, Hoyt J, McWhinnie E, Chirn G-W, Tao CY, Tallarico JA, Labow M, Jenkins JL, Mitchison TJ et al (2007) Integrating high-content screening and ligand-target prediction to identify mechanism of action. Nat Chem Biol 4:59–68. (PMID: 10.1038/nchembio.2007.5318066055) Yu X, Tang L, Rao Y, Huang T, Zhou J & Lu J (2022) Point-BERT: Pre-training 3D point cloud transformers with masked point modeling. In 2022 IEEE/CVF Conference on Computer Vision and Pattern Recognition (CVPR). IEEE. Yu Y, Mai Y, Zheng Y, Shi L (2024) Assessing and mitigating batch effects in large-scale omics studies. Genome Biol 25:254. (PMID: 10.1186/s13059-024-03401-93936324411447944) Zaritsky A, Jamieson AR, Welf ES, Nevarez A, Cillay J, Eskiocak U, Cantarel BL, Danuser G (2021) Interpretable deep learning uncovers cellular properties in label-free live cell images that are predictive of highly metastatic melanoma. Cell Syst 12:733–747.e6. (PMID: 10.1016/j.cels.2021.05.003340777088353662) Zhai X, Kolesnikov A, Houlsby N, Beyer L (2022) Scaling vision transformers. In: 2022 IEEE/CVF conference on computer vision and pattern recognition (CVPR). IEEE. Zhan X, Yin Y, Zhang H (2024) BERMAD: batch effect removal for single-cell RNA-seq data using a multi-layer adaptation autoencoder with dual-channel framework. Bioinformatics 40:btae127. (PMID: 10.1093/bioinformatics/btae1273843954510942801) Zhang X, Wang X, Shivashankar GV, Uhler C (2022) Graph-based autoencoder integrates spatial transcriptomics with chromatin images and identifies joint biomarkers for Alzheimer’s disease. Nat Commun 13:1–17. Zhao Y, Wong L, Goh WWB (2020) How to do quantile normalization correctly for gene expression data analyses. Sci Rep 10:1–11. Zhou Y, Sollmann J, Chen J (2024) Deep-learning-based image compression for microscopy images: an empirical study. Biol Imaging 4:e16. (PMID: 10.1017/S2633903X240001513977660911704128) Ziemann M, Poulain P, Bora A (2023) The five pillars of computational reproducibility: bioinformatics and beyond. Brief Bioinform 24:bbad375. (PMID: 10.1093/bib/bbad3753787028710591307) |
| Grant Information: | T15LM009451 HHS | NIH | U.S. National Library of Medicine (NLM); 5T15LM007359 HHS | NIH | U.S. National Library of Medicine (NLM); R35 GM122547 United States GM NIGMS NIH HHS; RGY0081/2019 Human Frontier Science Program (HFSP); 923014 Gilbert Family Foundation (GFF); 23-28306 Alex's Lemonade Stand Foundation for Childhood Cancer (ALSF); 24CSA1255857 American Heart Association (AHA); DAF2021-225261 Chan Zuckerberg Initiative (CZI); MC_ST_00035 UKRI | Medical Research Council (MRC); MR/Ro15635/1 UKRI | Medical Research Council (MRC); 2348683 National Science Foundation (NSF); 10.13039/100014989 Silicon Valley Community Foundation |
| Contributed Indexing: | Keywords: Cell Profiling; Deep Learning; Feature Extraction; Image-Based Profiling; Phenotypic Screening |
| Entry Date(s): | Date Created: 20260328 Date Completed: 20260713 Latest Revision: 20260713 |
| Update Code: | 20260714 |
| PubMed Central ID: | PMC13144522 |
| DOI: | 10.1038/s44320-026-00197-7 |
| PMID: | 41896452 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1744-4292 |
|---|---|
| DOI: | 10.1038/s44320-026-00197-7 |