TY - JOUR T1 - Inference of single cell profiles from histology stains with the Single-Cell omics from Histology Analysis Framework (SCHAF) JF - bioRxiv DO - 10.1101/2023.03.21.533680 SP - 2023.03.21.533680 AU - Charles Comiter AU - Eeshit Dhaval Vaishnav AU - Metamia Ciampricotti AU - Bo Li AU - Yiming Yang AU - Scott J. Rodig AU - Madison Turner AU - Kathleen L. Pfaff AU - Judit Jané-Valbuena AU - Michal Slyper AU - Julia Waldman AU - Sebastian Vigneau AU - Jingyi Wu AU - Timothy R. Blosser AU - Åsa Segerstolpe AU - Daniel Abravanel AU - Nikil Wagle AU - Xiaowei Zhuang AU - Charles M. Rudin AU - Johanna Klughammer AU - Orit Rozenblatt-Rosen AU - Koseki J. Kobayash-Kirschvink AU - Jian Shu AU - Aviv Regev Y1 - 2023/01/01 UR - http://biorxiv.org/content/early/2023/03/23/2023.03.21.533680.abstract N2 - Tissue biology involves an intricate balance between cell-intrinsic processes and interactions between cells organized in specific spatial patterns, which can be respectively captured by single-cell profiling methods, such as single-cell RNA-seq (scRNA-seq), and histology imaging data, such as Hematoxylin-and-Eosin (H&E) stains. While single-cell profiles provide rich molecular information, they can be challenging to collect routinely and do not have spatial resolution. Conversely, histological H&E assays have been a cornerstone of tissue pathology for decades, but do not directly report on molecular details, although the observed structure they capture arises from molecules and cells. Here, we leverage adversarial machine learning to develop SCHAF (Single-Cell omics from Histology Analysis Framework), to generate a tissue sample’s spatially-resolved single-cell omics dataset from its H&E histology image. We demonstrate SCHAF on two types of human tumors—from lung and metastatic breast cancer—training with matched samples analyzed by both sc/snRNA-seq and by H&E staining. SCHAF generated appropriate single-cell profiles from histology images in test data, related them spatially, and compared well to ground-truth scRNA-Seq, expert pathologist annotations, or direct MERFISH measurements. SCHAF opens the way to next-generation H&E2.0 analyses and an integrated understanding of cell and tissue biology in health and disease.Competing Interest StatementAR is a co-founder and equity holder of Celsius Therapeutics, an equity holder in Immunitas, and until July 31, 2020 was an SAB member of ThermoFisher Scientific, Syros Pharmaceuticals, Neogene Therapeutics, and Asimov. From August 1, 2020, AR is an employee of Genentech and 33 has equity in Roche. JS is a scientific advisor for Arcadia Science. CMR has consulted regarding oncology drug development with AbbVie, Amgen, AstraZeneca, D2G, Daiichi Sankyo, Epizyme, Genentech/Roche, Ipsen, Jazz, Kowa, Lilly, Merck, and Syros. He serves on the scientific advisory boards of Bridge Medicines, Earli, and Harpoon Therapeutics. EDV is the founder of Sequome, Inc. BL, YY, ORR, and NW are employees as of 9 August 2021, 7 June 2021,19 October 2020, and Feb 13, 2023, respectively and have equity in Roche. SJR receives research support from Bristol-Myers-Squibb and KITE/Gilead. SJR is a member of the SAB of Immunitas Therapeutics. NW is an equity holder in Relay Therapeutics and a consultant and equity holder in Flare Therapeutic. Prior to Jan 31 2023 he was an SAB member of Relay Therapeutics, an advisory board member for Eli Lilly, and received research support from Astra-Zeneca and Puma Biotechnologies. MC is an employee of Mission Bio as of 22 February 2022. A patent application has been filed related to this work through Broad Institute. ER -