RetroExplorer: An Interactive Database of Endogenous Retroviruses in the Human Genome

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Within the human genome reside thousands of Endogenous Retroviruses (ERVs). Over 30 families of ERVs have entered the human germline. Most ERVs now remain inactive due to accumulation of mutations, but some ERVs retain the capacity to produce viral RNA, proteins and virions. My goal is to expand the bioinformatics arm of my research program by developing HQP and projects reliant on a currently unavailable resource - an interactive database of ERVs in the human genome. Several online databases were key in the identification and analysis of ERV sequences in the human genome - all these resources are now outdated or have left the internet. Clearly, there is a need for a modern and functional ERV database to provide researchers a platform from which to study these viruses. It is timely that my research group develops an online ERV database because: 1) no other online resources exist at the moment, 2) NCBI has just released a major human genome build GRCh38, and 3) there is a growing interest in ERV research, as they are increasingly associated with biological outcomes. My team is well suited to initiate this task, as we have developed in-house bioinformatic annotation of many ERVK sequences in the human genome. Over the next five years, we will roll-out this program in two phases: Phase 1 (Years 1-2): Annotation of ERV sequences within the human genome using the newly released human genome build GRCh38 and initial release of web-enabled RetroExplorer database. We will annotate and visually represent ERV sequences, linking to NCBI accession numbers, current nomenclature, as well as alternative names. The retroviral genes and functional elements will be labeled, and links to relevant NCBI databases provided. We will also list the flanking human genes that may be regulated by the retroviral LTRs and their NCBI Genes link. All information will be housed in a core database framework and hosted on an interactive website. Phase 2 (Years 3-5): Enhancement of RetroExplorer database features. Once the core platform is web-enabled, we will strive to include features absent from previous ERV databases, such as ERV insertional and single-nucleotide polymorphisms, viral protein functionality based on molecular biology screening assays, annotation of viral enzyme active sites and conserved motifs, transcription factor binding sites in ERV LTRs, and ERV family consensus sequence alignments. Another key feature will include links to relevant original literature for each ERV. This bioinformatics program will complement and extend my existing research, allowing future studies to have a solid basis in ERV nomenclature, position within the human genome and appreciation for the inherent functionality of these genomic parasites. Other researchers will benefit from the open-access database; it will provide a shared platform from which to initiate collaborations and promote research in this understudied area of retrovirology.