BIORXIV . ORG {}

We are analyzing https://www.biorxiv.org/content/10.1101/2023.03.21.533680v2.

Title:
Inference of single cell profiles from histology stains with the Single Cell omics from Histology Analysis Framework (SCHAF) | bioRxiv
Description:
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 spatial transcriptomics, 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 in the clinic and either lack spatial resolution or high gene throughput. 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 vision transformers and adversarial deep learning to develop the Single Cell omics from Histology Analysis Framework (SCHAF), which generates a tissue sample’s spatially-resolved whole transcriptome single cell omics dataset from its H&E histology image. We demonstrate SCHAF on a variety of tissues— including lung cancer, metastatic breast cancer, placentae, and whole mouse pups—training with matched samples analyzed by sc/snRNA-seq, H&E staining, and, when available, spatial transcriptomics. 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 spatial transcriptomic measurements, with some limitations. SCHAF opens the way to next-generation H&E analyses and an integrated understanding of cell and tissue biology in health and disease. ### Competing Interest Statement AR is a co-founder and was equity holder of Celsius Therapeutics, is 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 has equity in Roche. JS is a scientific advisor for Johnson & Johnson. A patent application has been filed related to this work through Broad Institute. CMR has consulted regarding oncology drug development with AbbVie, Amgen, AstraZeneca, Daiichi Sankyo, Genentech/Roche, Jazz, and Novartis. He serves on the scientific advisory boards of Auron, DISCO, and Earli and has received licensing fees and royalties related to DLL3-directed therapeutics. EDV is the founder & CEO of Sequome, Inc. BL, YY, ORR, and NW are employees of Genentech 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 Tempus AI as of 2 October 2023. AQV is an employee of AstraZeneca as of 17 July 2024.
Website Age:
12 years and 2 months (reg. 2013-04-08).