Manlio De Domenico
ScienceOpenš£ New Article from Network and Systems Medicine on #ScienceOpen!
šš 'Identification of Transcriptional Regulators Using a Combined Disease Module Identification and Prize-Collecting Steiner Tree Approach' ā”ļø https://drugrepocentral.scienceopen.com/hosted-document?doi=10.14293/NSM.25.1.0003
#REPO4EU #NetworkMedicine #Bioinformatics #TranscriptionFactors
Identification of Transcriptional Regulators Using a Combined Disease Module Identification and Prize-Collecting Steiner Tree Approach
<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d4991e168">Transcription factors play important roles in maintaining normal biological function, and their dysregulation can lead to the development of diseases. Identifying candidate transcription factors involved in disease pathogenesis is thus an important task for deriving mechanistic insights from gene expression data. We developed Transcriptional Regulator Identification using Prize-collecting Steiner trees (TRIPS), a workflow for identifying candidate transcriptional regulators from caseācontrol expression data. In the first step, TRIPS combines the results of differential expression analysis with a disease module identification step to retrieve perturbed subnetworks comprising an expanded gene list. TRIPS then solves a prize-collecting Steiner tree problem on a gene regulatory network, thereby identifying candidate transcriptional modules and transcription factors. We compare TRIPS to relevant methods using publicly available disease datasets and show that the proposed workflow can recover known disease-associated transcription factors with high precision. Network perturbation analyses demonstrate the reliability of TRIPS results. We further evaluate TRIPS on Alzheimerās disease, diabetic kidney disease, and prostate cancer single-cell omics datasets. Overall, TRIPS is a useful approach for prioritizing transcriptional mechanisms for further downstream analyses. </p>
CSBJ
Luis M. Rocha
Luis M. Rocha
