Title
Dhaka: Variational Autoencoder For Unmasking Tumor Heterogeneity From Single Cell Genomic Data
Abstract
Motivation: Intra-tumor heterogeneity is one of the key confounding factors in deciphering tumor evolution. Malignant cells exhibit variations in their gene expression, copy numbers and mutation even when originating from a single progenitor cell. Single cell sequencing of tumor cells has recently emerged as a viable option for unmasking the underlying tumor heterogeneity. However, extracting features from single cell genomic data in order to infer their evolutionary trajectory remains computationally challenging due to the extremely noisy and sparse nature of the data.Results: Here we describe 'Dhaka', a variational autoencoder method which transforms single cell genomic data to a reduced dimension feature space that is more efficient in differentiating between (hidden) tumor subpopulations. Our method is general and can be applied to several different types of genomic data including copy number variation from scDNA-Seq and gene expression from scRNA-Seq experiments. We tested the method on synthetic and six single cell cancer datasets where the number of cells ranges from 250 to 6000 for each sample. Analysis of the resulting feature space revealed subpopulations of cells and their marker genes. The features are also able to infer the lineage and/or differentiation trajectory between cells greatly improving upon prior methods suggested for feature extraction and dimensionality reduction of such data.
Year
DOI
Venue
2021
10.1093/bioinformatics/btz095
BIOINFORMATICS
DocType
Volume
Issue
Journal
37
11
ISSN
Citations 
PageRank 
1367-4803
0
0.34
References 
Authors
0
4
Name
Order
Citations
PageRank
Sabrina Rashid1224.00
Sohrab P. Shah233724.09
Ziv Bar-Joseph31207112.00
Ravi Pandya4502.68