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10.3390/ijms23073962
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Article

Applying Protein–Protein Interactions and Complex Networks to Identify Novel Genes in Retinitis Pigmentosa Pathogenesis

by
Su-Bin Yoon
,
Yu-Chien (Calvin) Ma
,
Akaash Venkat
,
Chun-Yu (Audi) Liu
and
Jie J. Zheng
*
Department of Ophthalmology, Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2022, 23(7), 3962; https://doi.org/10.3390/ijms23073962
Submission received: 27 February 2022 / Revised: 29 March 2022 / Accepted: 29 March 2022 / Published: 2 April 2022
(This article belongs to the Special Issue Genetics and Epigenetics of Eye Diseases)
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Abstract

Retinitis Pigmentosa (RP) is a hereditary retinal disorder that causes the atrophy of photoreceptor rod cells. Since individual defective genes converge on the same disease, we hypothesized that all causal genes of RP belong in a complex network. To explore this hypothesis, we conducted a gene connection analysis using 161 genes attributed to RP, compiled from the Retinal Information Network, RetNet. We then examined the protein interaction network (PIN) of these genes. In line with our hypothesis, using STRING, we directly connected 149 genes out of the recognized 159 genes. To uncover the association between the PIN and the ten unrecalled genes, we developed an algorithm to pinpoint the best candidate genes to connect the uncalled genes to the PIN and identified ten such genes. We propose that mutations within these ten genes may also cause RP; this notion is supported by analyzing and categorizing the known causal genes based on cellular locations and related functions. The successful establishment of the PIN among all documented genes and the discovery of novel genes for RP strongly suggest an interconnectedness that causes the disease on the molecular level. In addition, our computational gene search protocol can help identify the genes and loci responsible for genetic diseases, not limited to RP.
Keywords: Retinitis Pigmentosa; retinal degeneration; protein interaction network (PIN); protein–protein interaction (PPI); complex networks; network medicine; bioinformatics; STRING Retinitis Pigmentosa; retinal degeneration; protein interaction network (PIN); protein–protein interaction (PPI); complex networks; network medicine; bioinformatics; STRING

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MDPI and ACS Style

Yoon, S.-B.; Ma, Y.-C.; Venkat, A.; Liu, C.-Y.; Zheng, J.J. Applying Protein–Protein Interactions and Complex Networks to Identify Novel Genes in Retinitis Pigmentosa Pathogenesis. Int. J. Mol. Sci. 2022, 23, 3962. https://doi.org/10.3390/ijms23073962

AMA Style

Yoon S-B, Ma Y-C, Venkat A, Liu C-Y, Zheng JJ. Applying Protein–Protein Interactions and Complex Networks to Identify Novel Genes in Retinitis Pigmentosa Pathogenesis. International Journal of Molecular Sciences. 2022; 23(7):3962. https://doi.org/10.3390/ijms23073962

Chicago/Turabian Style

Yoon, Su-Bin, Yu-Chien (Calvin) Ma, Akaash Venkat, Chun-Yu (Audi) Liu, and Jie J. Zheng. 2022. "Applying Protein–Protein Interactions and Complex Networks to Identify Novel Genes in Retinitis Pigmentosa Pathogenesis" International Journal of Molecular Sciences 23, no. 7: 3962. https://doi.org/10.3390/ijms23073962

APA Style

Yoon, S.-B., Ma, Y.-C., Venkat, A., Liu, C.-Y., & Zheng, J. J. (2022). Applying Protein–Protein Interactions and Complex Networks to Identify Novel Genes in Retinitis Pigmentosa Pathogenesis. International Journal of Molecular Sciences, 23(7), 3962. https://doi.org/10.3390/ijms23073962

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