HAHmiR.DB: A server platform for high-altitude human miRNA-gene coregulatory networks and associated regulatory circuits

Abstract

Around 140 million people live in high-altitude (HA) conditions! and even a larger number visit such places for tourism, adventure-seeking or sports training. Rapid ascent to HA can cause severe damage to the body organs and may lead to many fatal disorders. During induction to HA, human body undergoes various physiological, biochemical, hematological and molecular changes to adapt to the extreme environmental conditions. Several literature references hint that gene-expression-regulation and regulatory molecules like miRNAs and transcription factors (TFs) control adaptive responses during HA stress. These biomolecules are known to interact in a complex combinatorial manner to fine-tune the gene expression and help in controlling the molecular responses during this stress and ultimately help in acclimatization. High-Altitude Human miRNA Database (HAHmiR.DB) is a unique, comprehensive and curated collection of miRNAs that have been experimentally validated to be associated with HA stress, their level of expression in different altitudes, fold change, experiment duration, biomarker association, disease and drug association, tissue-specific expression level, Gene Ontology (GO) and Kyoto Encyclopaedia of Gene and Genomes (KEGG) pathway associations. As a server platform, it also uniquely constructs and analyses interactive miRNA-TF-gene coregulatory networks and extracts regulatory circuits/feed-forward loops (FFLs). These regulatory circuits help to offer mechanistic insights into complex regulatory mechanisms during HA stress. The server can also build these regulatory networks between two and more miRNAs of the database and also identify the regulatory circuits from this network. Hence, HAHmiR.DB is the first-of-its-kind database in HA research, which is a reliable platform to explore, compare, analyse and retrieve miRNAs associated with HA stress, their coregulatory networks and FFL regulatory-circuits. HAHmiR.DB is freely accessible at http://www.hahmirdb.in.