A novel integrative multi-omics approach to unravel the genetic determinants of rare diseases with application in sinusoidal obstruction syndrome.

ABSTRACT:

Background

Genotype-phenotype analyses of rare diseases often suffer from a lack of power, due to small sample size, which makes identifying significant associations difficult. Sinusoidal obstruction syndrome (SOS) of the liver is a rare but life-threatening complication of hematopoietic stem cell transplantation (HSCT). The alkylating agent busulfan is commonly used in HSCT and known to trigger SOS. We developed a novel pipeline to identify genetic determinants in rare diseases by combining in vitro information with clinical whole-exome sequencing (WES) data and applied it in SOS patients and controls.

Methods

First, we analysed differential gene expression in six lymphoblastoid cell lines (LCLs) before and after incubation with busulfan. Second, we used WES data from 87 HS

SUBMITTER: Waespe N 

PROVIDER: S-EPMC10075428 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature