Applying Protein–Protein Interactions and Complex Networks to Identify Novel Genes in Retinitis Pigmentosa Pathogenesis
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 conne...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-04-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/7/3962 |
| _version_ | 1797438964887453696 |
|---|---|
| author | Su-Bin Yoon Yu-Chien (Calvin) Ma Akaash Venkat Chun-Yu (Audi) Liu Jie J. Zheng |
| author_facet | Su-Bin Yoon Yu-Chien (Calvin) Ma Akaash Venkat Chun-Yu (Audi) Liu Jie J. Zheng |
| author_sort | Su-Bin Yoon |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T11:44:53Z |
| format | Article |
| id | doaj.art-d1272085e1b141daa4cba60f9ef5817f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T11:44:53Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d1272085e1b141daa4cba60f9ef5817f2023-11-30T23:24:37ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01237396210.3390/ijms23073962Applying Protein–Protein Interactions and Complex Networks to Identify Novel Genes in Retinitis Pigmentosa PathogenesisSu-Bin Yoon0Yu-Chien (Calvin) Ma1Akaash Venkat2Chun-Yu (Audi) Liu3Jie J. Zheng4Department of Ophthalmology, Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USADepartment of Ophthalmology, Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USADepartment of Ophthalmology, Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USADepartment of Ophthalmology, Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USADepartment of Ophthalmology, Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USARetinitis 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.https://www.mdpi.com/1422-0067/23/7/3962Retinitis Pigmentosaretinal degenerationprotein interaction network (PIN)protein–protein interaction (PPI)complex networksnetwork medicine |
| spellingShingle | Su-Bin Yoon Yu-Chien (Calvin) Ma Akaash Venkat Chun-Yu (Audi) Liu Jie J. Zheng Applying Protein–Protein Interactions and Complex Networks to Identify Novel Genes in Retinitis Pigmentosa Pathogenesis International Journal of Molecular Sciences Retinitis Pigmentosa retinal degeneration protein interaction network (PIN) protein–protein interaction (PPI) complex networks network medicine |
| title | Applying Protein–Protein Interactions and Complex Networks to Identify Novel Genes in Retinitis Pigmentosa Pathogenesis |
| title_full | Applying Protein–Protein Interactions and Complex Networks to Identify Novel Genes in Retinitis Pigmentosa Pathogenesis |
| title_fullStr | Applying Protein–Protein Interactions and Complex Networks to Identify Novel Genes in Retinitis Pigmentosa Pathogenesis |
| title_full_unstemmed | Applying Protein–Protein Interactions and Complex Networks to Identify Novel Genes in Retinitis Pigmentosa Pathogenesis |
| title_short | Applying Protein–Protein Interactions and Complex Networks to Identify Novel Genes in Retinitis Pigmentosa Pathogenesis |
| title_sort | applying protein protein interactions and complex networks to identify novel genes in retinitis pigmentosa pathogenesis |
| topic | Retinitis Pigmentosa retinal degeneration protein interaction network (PIN) protein–protein interaction (PPI) complex networks network medicine |
| url | https://www.mdpi.com/1422-0067/23/7/3962 |
| work_keys_str_mv | AT subinyoon applyingproteinproteininteractionsandcomplexnetworkstoidentifynovelgenesinretinitispigmentosapathogenesis AT yuchiencalvinma applyingproteinproteininteractionsandcomplexnetworkstoidentifynovelgenesinretinitispigmentosapathogenesis AT akaashvenkat applyingproteinproteininteractionsandcomplexnetworkstoidentifynovelgenesinretinitispigmentosapathogenesis AT chunyuaudiliu applyingproteinproteininteractionsandcomplexnetworkstoidentifynovelgenesinretinitispigmentosapathogenesis AT jiejzheng applyingproteinproteininteractionsandcomplexnetworkstoidentifynovelgenesinretinitispigmentosapathogenesis |