Integrative Modeling and Novel Technologies in Human Genomics

Abstract In this chapter a brief description of DNA sequencing technologies is presented, along with their practical applications for human genomics studies. The functional assessment of human genes and genetic variants, and their involvement in pathological processes requires combinatorial use of molecular information (sometimes available in human databases) with model systems that allow comparing candidate variants to other variants at the locus of interest. The identification of patients with similar phenotypes and genotypes across different platforms facilitates prioritization of genes and variants. Bioinformatic tools that further assist prioritization of genetic variants integrating various genomic and epigenomic annotations are also instrumental for the necessary understanding of gene regulatory networks that underlie human biology and disease. The use of computational tools and methodologies such as single-cell molecular analyses, in addition to model system-derived data, are discussed as a way to gain a more complete understanding of genotype–phenotype relations.