Releases: cistrome/MIRA
CODAL Nature Communications, 2023
Multi-batch Single Cell Comparative Atlas Construction by Deep Learning Disentanglement
Allen W. Lynch1,2, Myles Brown3,4, and Clifford A. Meyer2,3,5,*
Nature Communications, 2023
1 Department of Biomedical Informatics, Harvard Medical School, Boston MA, USA
2 Department of Data Science, Dana-Farber Cancer Institute, Boston MA, USA.
3 Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.
4 Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
5 Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
*Correspondence to: cliff_meyer@ds.dfci.harvard.edu
Abstract
Cell state atlases constructed through single cell RNA-seq and ATAC-seq analysis are powerful tools for analyzing the effects of genetic and drug treatment-induced perturbations on complex cell systems. Comparative analysis of such atlases can yield new insights into cell state and trajectory alterations. Perturbation experiments often require that single cell assays be carried out in multiple batches, which can introduce technical distortions that confound the comparison of biological quantities between different batches. Here we propose CODAL, a variational autoencoder-based statistical model which uses a novel mutual information regularization technique to explicitly disentangle factors related to technical and biological effects. We demonstrate CODAL’s capacity for batch-confounded cell type discovery when applied to simulated datasets and embryonic development atlases with gene knockouts. CODAL improves the representation of RNA-seq and ATAC-seq modalities, yields interpretable modules of biological variation, and enables the generalization of other count-based generative models to multi-batched data.
MIRA version 1
Version 1 of MIRA, as originally released. Version 2, which will be released upon publication of "CODAL", will supplant version 1 with extensions and improvements to many core features.
0.0.0a1
Merge branch 'main' of https://github.com/AllenWLynch/MIRA into main Merging from v0.0.0 development.