Multiomics Integration at Single-Cell Resolution Using Bayesian Networks: A Case Study in Hepatocellular Carcinoma

Multiomics data integration is one of the leading frontiers of complex disease research and integrative biology. The advances in single-cell sequencing technologies offer yet another crucial dimension in multiomics research. The single-cell studies enable the study and integration of multiomics data simultaneously in the same cell. We report in this study multiomics data integration in single-cell resolution using Bayesian networks (BNs) in a case study of hepatocellular carcinoma (HCC). A BN encodes the conditional dependencies/independencies of variables using a graphical model with an accompanying joint probability. RNA-seq and Reduced Representation Bisulfite Sequencing data were analyzed separately, and copy number variations were estimated by the hidden Markov model method. Several BN models were constructed to reveal omics' causal and associational relationships. These methods were subjected to a validation study using an independent data set. We show the heterogeneity of the multiple cellular layers of HCC at single-cell omics resolution by identifying best-fitted BN models of 295 genes. We also provide novel insights into the multiomics mechanistic relationships in the human lymphocyte antigen class I genes in HCC. To the best of our knowledge, this is the first study to focus on integrating omics data using a machine learning algorithm, BNs, at the single-cell resolution using a case study of HCC.