IGAP- Integrative Genome Analysis Pipeline Reveals New Gene Regulatory Model Associated with Nonspecific TF-DNA Binding Affinity

Oslo University Hospital This work was supported by the South-Eastern Norway Regional Health Authority

Authors

Alireza Sahaf Naeini1, Amna Farooq1, Magnar Bjørås2, and Junbai Wang1

1Department of Pathology, Norwegian Radium Hospital, PO Box 4953 Nydalen, 0424 Oslo, Norway

2Department of Cancer Res and Molecular Medicine, Norwegian University of Science and Technology (NTNU), N-7489 Trondheim, Norway

Introduction

Human genome is a regulatory jungle where regulation happens in multi-dimensional fashion. While biophysical factors like Non-specific Transcription factor Binding Affinity (nTBA) act prior to sequence level, there are factors acting at sequence level of genome and above sequence level as well. Sequence level regulatory features like enhancers, Transcription Start Site, and High Occupancy Target (HOT) regions may play equally important role in genome regulation along above sequence level features like histone modifications and intra-chromosomal interactions. This multidimensionality of regulation compels inclusion of maximum factors for proper understanding of regulatory landscape of human genome. However, complex nature of TF-DNA binding makes nTBA calculation a computationally exhaustive task. We present here a robust algorithm for calculation of nTBA. In order to integrate major biophysical, genetic and epigenetic features involved in genome regulation, we also present a user-friendly package Integrative Genome Analysis Pipeline (IGAP). This integrative approach not only helped us to segregate highly Active Genomic Zones but also lead us to discover a novel gene regulatory model explaining nTBA and HOT guided search for true transcription factor binding site.

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