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

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

Solo LTRs used in the enrichment analysis in EnHERV.

<p>Solo LTRs used in the enrichment analysis in EnHERV.</p

The enrichment analysis page.

<p>EnHERV’s enrichment analysis page. EnHERV gives the Fisher’s exact, P-value and odd ratio of the designed enrichment analysis. EnHERV also provides parallel analysis for sub-selected HERV superfamily/family.</p

HERV truncation pattern distribution.

<p>Percentage and number of each HERV truncation pattern in the HERV elements resulting from the defragmentation process.</p

Number of defragmented and non-defragmented elements.

<p>Graph shows a number of defragmented and non-defragmented elements in relation to distance parameters.</p

HERV superfamily distribution.

<p>Percentage and number of copy of each HERV superfamily in hg19/GRCh37 genome. 687,420 HERV elements were distributed into 5 groups including 4 superfamilies and one unclassified group. Almost 50% of HERV elements in the human genome belongs to the ERVL-MaLR superfamily.</p

The number of defragmented elements, resulting from HERV defragmentation using REannotate with different values of distance parameters, and their coverage percentages.

<p>The number of defragmented elements, resulting from HERV defragmentation using REannotate with different values of distance parameters, and their coverage percentages.</p