ACE2 Netlas: In-silico functional characterization and drug-gene interactions of ACE2 gene network to understand its potential involvement in COVID-19 susceptibility
Abstract Angiotensin-converting enzyme-2 (ACE2) receptor has been identified as the key adhesion molecule for the transmission of the SARS-CoV-2. However, there is no evidence that human genetic variation in ACE2 is singularly responsible for COVID-19 susceptibility. Therefore, we performed a multi-level characterization of genes that interact with ACE2 (ACE2-gene network) for their over-represented biological properties in the context of COVID-19.The phenome-wide association of 51 genes including ACE2 with 4,756 traits categorized into 26 phenotype categories, showed enrichment of immunological, respiratory, environmental, skeletal, dermatological, and metabolic domains (p<4e-4). Transcriptomic regulation of ACE2-gene network was enriched for tissue-specificity in kidney, small intestine, and colon (p<4.7e-4). Leveraging the drug-gene interaction database we identified 47 drugs, including dexamethasone and spironolactone, among others.Considering genetic variants within ± 10 kb of ACE2-network genes we characterized functional consequences (among others) using miRNA binding-site targets. MiRNAs affected by ACE2-network variants revealed statistical over-representation of inflammation, aging, diabetes, and heart conditions. With respect to variants mapped to the ACE2-network, we observed COVID-19 related associations in RORA, SLC12A6 and SLC6A19 genes.Overall, functional characterization of ACE2-gene network highlights several potential mechanisms in COVID-19 susceptibility. The data can also be accessed at <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://gpwhiz.github.io/ACE2Netlas/">https://gpwhiz.github.io/ACE2Netlas/</jats:ext-link>.
| Medienart: |
|
|---|
Preprint| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
bioRxiv.org - (2021) vom: 15. Dez. Zur Gesamtaufnahme - year:2021 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Pathak, Gita A [VerfasserIn] |
|---|
| Links: |
|---|
| doi: |
10.1101/2020.10.27.20220665 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
XBI019234252 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | XBI019234252 | ||
| 003 | DE-627 | ||
| 005 | 20230429084938.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 201030s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2020.10.27.20220665 |2 doi | |
| 035 | |a (DE-627)XBI019234252 | ||
| 035 | |a (biorXiv)10.1101/2020.10.27.20220665 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | |a 570 |q DE-84 | |
| 100 | 1 | |a Pathak, Gita A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a ACE2 Netlas: In-silico functional characterization and drug-gene interactions of ACE2 gene network to understand its potential involvement in COVID-19 susceptibility |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Abstract Angiotensin-converting enzyme-2 (ACE2) receptor has been identified as the key adhesion molecule for the transmission of the SARS-CoV-2. However, there is no evidence that human genetic variation in ACE2 is singularly responsible for COVID-19 susceptibility. Therefore, we performed a multi-level characterization of genes that interact with ACE2 (ACE2-gene network) for their over-represented biological properties in the context of COVID-19.The phenome-wide association of 51 genes including ACE2 with 4,756 traits categorized into 26 phenotype categories, showed enrichment of immunological, respiratory, environmental, skeletal, dermatological, and metabolic domains (p<4e-4). Transcriptomic regulation of ACE2-gene network was enriched for tissue-specificity in kidney, small intestine, and colon (p<4.7e-4). Leveraging the drug-gene interaction database we identified 47 drugs, including dexamethasone and spironolactone, among others.Considering genetic variants within ± 10 kb of ACE2-network genes we characterized functional consequences (among others) using miRNA binding-site targets. MiRNAs affected by ACE2-network variants revealed statistical over-representation of inflammation, aging, diabetes, and heart conditions. With respect to variants mapped to the ACE2-network, we observed COVID-19 related associations in RORA, SLC12A6 and SLC6A19 genes.Overall, functional characterization of ACE2-gene network highlights several potential mechanisms in COVID-19 susceptibility. The data can also be accessed at <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://gpwhiz.github.io/ACE2Netlas/">https://gpwhiz.github.io/ACE2Netlas/</jats:ext-link> | ||
| 700 | 1 | |a Wendt, Frank R |e verfasserin |4 aut | |
| 700 | 1 | |a Goswami, Aranyak |e verfasserin |4 aut | |
| 700 | 1 | |a De Angelis, Flavio |e verfasserin |4 aut | |
| 700 | 1 | |a Polimanti, Renato |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv.org |g (2021) vom: 15. Dez. |
| 773 | 1 | 8 | |g year:2021 |g day:15 |g month:12 |
| 856 | 4 | 0 | |u https://doi.org/10.3389/fgene.2021.698033 |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2020.10.27.20220665 |z kostenfrei |3 Volltext |
| 912 | |a GBV_XBI | ||
| 912 | |a SSG-OLC-PHA | ||
| 951 | |a AR | ||
| 952 | |j 2021 |b 15 |c 12 | ||
| 953 | |2 045F |a 570 | ||