Data mining and network analysis reveals C-X-C chemokine receptor type 5 is involved in the pathophysiology of age-related macular degeneration

Abstract

Our previous studies found that the C-X-C motif chemokine receptor 5 (CXCR5) loss leads to retinal pigment epithelium (RPE) dysfunction and AMD pathogenesis. The current study aimed to characterize the G protein-coupled receptor (GPCR) structure of CXCR5 and analyze its interactions with AMD-related risk genes. The sequence alignments, homology model of CXCR5 and structural assessment analysis were performed. Data and text mining were then performed to identify AMD-related risk genes and their interaction with CXCR5 using statistical and mathematical algorithms. Sequence alignment and phylogenetic tree analysis revealed that human CXCR5 was highly similar (85.4839%) to the rabbit. The least similarity (33.871%) was found to be in zebrafish compared to the other species. The CXCR5 model structural assessment and secondary structure analysis exhibited an excellent model. Network analysis revealed that IL10, TNF, ICAM1, CXCL1, CXCL8, APP, TLR4, SELL, C3, IL17A and CCR2 were the most connected genes CXCR5. These findings suggest that CXCR5 signaling may regulate the biological function of RPE and modulate AMD pathophysiology via GPCR signaling and interacting with identified AMD risk genes. In summary, the data presented here provide novel and crucial insights into the molecular mechanisms of CXCR5 involvement in AMD.

Communicated by Ramaswamy H. Sarma

Keywords:

• CXCR5
• AMD
• sequence analysis
• homology modeling
• data mining

Acknowledgements

The authors wish to acknowledge the contribution of the Division of Information Technology (UM system) University of Missouri (Columbia, MO, USA) for High-Performance Computing (HPC) facilities.

Disclosure statement

The authors have no conflict of interest to disclose in relation to this paper. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; in the decision to publish the results.

Data availability

All data generated and analyzed during this study are included in this published article and it’s Supporting Information.

Ethical information

All experiments and procedures are not involving the use of mice and other animals.

Authors’ contributions

Conceptualization, MSS and HH; methodology, MSS and HH; software, MSS; formal analysis, MS; investigation, HH and MSS; resources, HH; data curation, MSS and HH; writing—original draft preparation, MSS, and HH; writing—review and editing, MSS, AL, AM, XY, ST and HH; visualization, MSS; supervision, HH; project administration, HH; funding acquisition, HH, MSS and HH wrote the manuscript and critically revised it by MSS, AL, AM, XY, ST and HH. All authors reviewed and accepted the manuscript’s final version.

Additional information

Funding

Dr. Huang’s research is supported by NIH grants R01 (EY027824); Missouri University start-up fund (Hu Huang research group). Dr. Shibo Tang’s research is supported by NSFC fund (81870677).