WebHERV: A Web Server for the Computational Investigation of Gene Expression Associated With Endogenous...

Area of Science:

• Genomics
• Molecular Biology
• Bioinformatics

Background:

• Human endogenous retroviruses (HERVs) constitute a significant portion of the human genome, with their expression linked to various diseases.
• While most HERV sequences have lost protein-coding ability due to mutations, they can still influence adjacent gene expression and biological functions.
• Understanding HERV activity is crucial for disease research, particularly in areas like cancer and neurodegeneration.

Purpose of the Study:

• To develop a computational tool, WebHERV, for predicting active HERV-like sequences within the human genome.
• To identify potential active HERV candidates in Hodgkin lymphoma (HL) cell lines.
• To investigate the functional impact of HERV activity, including the identification of novel transcription start sites.

Main Methods:

• WebHERV server utilizes a comparison between user-uploaded expressed sequence coordinates and HERV coordinates stored in the DRUMS database.
• Computational prediction of active HERV-like sequences in Hodgkin lymphoma cell lines.
• Experimental validation of predicted HERV candidates using a modified SMART technique.

Main Results:

• WebHERV successfully predicted putative active HERV-like sequences in Hodgkin lymphoma cell lines.
• One validated HERV candidate was identified, demonstrating the tool's efficacy.
• A novel alternative transcription start site for the cytochrome P450, family 4, subfamily Z, polypeptide 1 (CYP4Z1) gene was discovered.

Conclusions:

• WebHERV is a valuable tool for the computational prediction of active HERV-like sequences.
• The study highlights the potential involvement of HERVs in Hodgkin lymphoma.
• The identification of a new transcription start site for CYP4Z1 underscores the functional impact of HERV elements.