EnHERV: Enrichment analysis of specific human endogenous retrovirus patterns and their neighboring genes

Abstract

Human endogenous retroviruses (HERVs) are flanked by long terminal repeats (LTRs), which contain the regulation part of the retrovirus. Remaining HERVs constitute 7% to 8% of the present day human genome, and most have been identified as solo LTRs. The HERV sequences have been associated with several molecular functions as well as certain diseases in human, but their roles in human diseases are yet to be established. We designed EnHERV to make accessible the identified endogenous retrovirus repetitive sequences from Repbase Update (a database of eukaryotic repetitive elements) that are present in the human genome. Defragmentation process was done to improve the RepeatMasker annotation output. The defragmented elements were used as core database in EnHERV. EnHERV is available at http://sysbio.chula.ac.th/enherv and can be searched using either gene lists of user interest or HERV characteristics. Besides the search function, EnHERV also provides an enrichment analysis function that allows users to perform enrichment analysis between selected HERV characteristics and user-input gene lists, especially genes with the expression profile of a certain disease. EnHERV will facilitate exploratory studies of specific HERV characteristics that control gene expression patterns related to various disease conditions. Here we analyzed 25 selected HERV groups/names from all four HERV superfamilies, using the sense and anti-sense directions of the HERV and gene expression profiles from 49 specific tissue and disease conditions. We found that intragenic HERVs were associated with down-regulated genes in most cancer conditions and in psoriatic skin tissues and associated with up-regulated genes in immune cells particularly from systemic lupus erythematosus (SLE) patients. EnHERV allowed the analysis of how different types of LTRs were differentially associated with specific gene expression profiles in particular disease conditions for further studies into their mechanisms and functions.

Endogenous retroviral signatures predict immunotherapy response in clear cell renal cell carcinoma

“…There exist several databases of hERV elements, including HERVd, which contains hERV-like elements, and their genomic locations that have been used for analysis of RNA-Seq data (16)(17)(18). Additionally, there are several tools for identification of intra-and intergenic hERV-like elements (19), related transposable elements (20), and interspersed repeats (RepeatMasker) among human transcripts (21). While these resources provide Human endogenous retroviruses (hERVs) are remnants of exogenous retroviruses that have integrated into the genome throughout evolution.…”

Alu siRNA to Increase Alu Element Methylation and Prevent DNA Damage

“…In human cells, small RNA was used to promote DNA methylation, shRNA for long interspersed element-1 (LINE-1) and hepatitis B virus, and siRNA for HIV-1 promoter region [11][12][13]. There are many types of IRS such as Alu elements, LINE-1, and human endogenous retrovirus [14][15][16][17]. To increase DNA methylation, we tested siRNA to unique sequences and several IRS sequences.…”

The contribution of HERV‐E clone 4‐1 and other HERV‐E members to the pathogenesis of rheumatic autoimmune diseases

“…HERV‐E appeared in primate genome 45 million years ago, after the divergence of prosimians and New World monkeys (76). HERV‐E members belong to the superfamily of ERV1 (http://herv.img.cas.cz/) that contributes for 25.15% to the whole HERV genetic make‐up in hg19/GRCh37 genome (77), and to the HERV‐E family that is characterized by the presence of a Glu‐tRNA as primer‐binding site specificity (78). These elements are included in the class I of the classification of human endogenous retroviruses, due to their similarity to gammaretrovirus, and have an antisense orientation, which confers a lower probability of being deleted and the property of positively or negatively modulating the neighboring genes (79‐81).…”