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Integration of single cell gene expression data in Bayesian association analysis of rare variants

Zhong, G.; Choi, Y. A.; Shen, Y.

2022-07-14 bioinformatics
10.1101/2022.05.13.491893 bioRxiv
Show abstract

We present VBASS, a Bayesian method that integrates single-cell expression and de novo variant (DNV) data to improve power of disease risk gene discovery. VBASS models disease risk prior as a function of expression profiles, approximated by deep neural networks. It learns the weights of neural networks and parameters of Poisson likelihood models of DNV counts jointly from expression and genetics data. On simulated data, VBASS shows proper error rate control and better power than state-of-the-art methods. We applied VBASS to published datasets and identified more candidate risk genes with supports from literature or data from independent cohorts.

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