EAPSI: Deciphering functionality of mutations across the human genome with respect to parental DNA contribution

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Every human genome consists of approximately 6.5 billion deoxyribose nucleic acid (DNA) bases organized into two sets of 23 chromosomes. Each individual receives one haploid set of chromosomes (n=23 chromosomes, ~3 billion DNA bases) from their mother and one set from their father upon fertilization, making a diploid genome. More effective methods accounting for diploid genome could help elucidate genome function and missing genome heritability in a number of genomic sub-disciplines including clinical genome annotation and complex disease studies. In collaboration with Dr. Ken Wing-Kin Sung at the National University of Singapore who has expertise in computational genomics, this research project will develop computational methods to uncover features dependent on the diploid nature of the human genome.Human genome sequencing technologies have rapidly advanced in recent years. However, accurate statistical and computational methods are needed to assign maternal or paternal specific (phase) function to individual mutations. Sequence analyses that take into account the phase-specific context of each variant by leveraging familial trios may uncover the functional effects of mutation combinations that would otherwise go undetected. The goal of this project is to provide a modular phase computational pipeline that can be adapted for datasets of sequenced trios, thus datasets where nuclear trios and extended pedigrees have been sequenced will be incorporated into this study. Currently, a preliminary 'functional phase' pipeline to analyze samples has been implemented in the programming languages Python and R. This early stage software has already uncovered novel insights regarding the frequency of phase-specific functional coding pairs and statistical determination of functional variants alleles in the available dataset. This NSF EAPSI award is funded in collaboration with the National Research Foundation of Singapore.