A New Biophysical Metric for Interrogating the Information Content in Human Genome Sequence Variation: Proof of Concept

TL;DR

This paper introduces the normalized information content (NIC), a new biophysical metric based on SNP haploblock variation, to better understand the functional significance of human genome variation and its role in host adaptation.

Contribution

The study develops and demonstrates NIC, a novel metric that links SNP haploblock variation to molecular pathways and regulatory elements in the human genome.

Findings

Low NIC haploblocks contain transcription factor binding sites and microRNA motifs.

NIC correlates with biochemical patterns in SNP variation.

NIC may help decode functional significance of genome variation.

Abstract

Various studies have shown an association between single nucleotide polymorphisms (SNPs) and common disease. We hypothesize that information encoded in the structure of SNP haploblock variation illumines molecular pathways and cellular mechanisms involved in the regulation of host adaptation to the environment. We developed and utilized the normalized information content (NIC), a novel metric based on SNP haploblock variation. We found that all SNP haploblocks with statistically low information content contained putative transcription factor binding sites and microRNA motifs. We were able to translate a biophysical, mathematical measure of common variants into a deeper understanding of the life sciences through analysis of biochemical patterns associated with SNP haploblock variation. We submit that this new metric, NIC, may be useful in decoding the functional significance of common variation in the human genome and in analyzing the regulation of molecular pathways involved in host adaptation to environmental pathogens.