In Silico Prediction of Hub Genes Involved in Diabetic Kidney and COVID-19 Related Disease by Differential Gene Expression and Interactome Analysis

Ulises Osuna-Martinez; Katia Aviña-Padilla; Vicente Olimon-Andalon; Carla Angulo-Rojo; Alma Guadron-Llanos; Jose Carlos Rivas-Ferreira; Francisco Urrea; Loranda Calderon-Zamora

doi:10.3390/genes13122412

In Silico Prediction of Hub Genes Involved in Diabetic Kidney and COVID-19 Related Disease by Differential Gene Expression and Interactome Analysis

Genes (Basel). 2022 Dec 19;13(12):2412. doi: 10.3390/genes13122412.

Authors

Ulises Osuna-Martinez¹, Katia Aviña-Padilla^{2

3}, Vicente Olimon-Andalon⁴, Carla Angulo-Rojo⁵, Alma Guadron-Llanos⁵, Jose Carlos Rivas-Ferreira⁶, Francisco Urrea⁷, Loranda Calderon-Zamora⁴

Affiliations

¹ Biological and Chemical Sciences Faculty, Autonomous University of Sinaloa, Calzada de las Americas y calle Universitarios, s/n. Ciudad Universitaria, Culiacan 80013, Mexico.
² Department of Crop Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
³ Centro de Investigacion y de Estudios Avanzados del I.P.N. Unidad Irapuato, Irapuato 36821, Mexico.
⁴ Biology Faculty, Autonomous University of Sinaloa, Calzada de las Americas y calle Universitarios, s/n. Ciudad Universitaria, Culiacan 80013, Mexico.
⁵ Medicine Faculty, Autonomous University of Sinaloa, Calle Sauces, Fraccionamiento Los Fresnos s/n, Culiacan 80019, Mexico.
⁶ Department of Gynecology and Obstetrics, Medicine Faculty, Universidad de Concepcion, Calle Janequeo esquina Avenida Chacabuco s/n, Concepcion 4030000, Chile.
⁷ Institute for Social Security and Services for State Workers, Regional Hospital, Heroico Colegio Militar s/n, 5 de Mayo, Culiacan 80230, Mexico.

Abstract

Diabetic kidney disease (DKD) is a frequently chronic kidney pathology derived from diabetes comorbidity. This condition has irreversible damage and its risk factor increases with SARS-CoV-2 infection. The prognostic outcome for diabetic patients with COVID-19 is dismal, even with intensive medical treatment. However, there is still scarce information on critical genes involved in the pathophysiological impact of COVID-19 on DKD. Herein, we characterize differential expression gene (DEG) profiles and determine hub genes undergoing transcriptional reprogramming in both disease conditions. Out of 995 DEGs, we identified 42 shared with COVID-19 pathways. Enrichment analysis elucidated that they are significantly induced with implications for immune and inflammatory responses. By performing a protein-protein interaction (PPI) network and applying topological methods, we determine the following five hub genes: STAT1, IRF7, ISG15, MX1 and OAS1. Then, by network deconvolution, we determine their co-expressed gene modules. Moreover, we validate the conservancy of their upregulation using the Coronascape database (DB). Finally, tissue-specific regulation of the five predictive hub genes indicates that OAS1 and MX1 expression levels are lower in healthy kidney tissue. Altogether, our results suggest that these genes could play an essential role in developing severe outcomes of COVID-19 in DKD patients.

Keywords: COVID-19; diabetic kidney disease; hub genes; in silico analysis; metabolic pathways; potential therapeutic.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

COVID-19* / genetics
Diabetes Mellitus*
Diabetic Nephropathies* / genetics
Gene Expression
Humans
Kidney
SARS-CoV-2

Grants and funding

This research was funded by CONACYT-FOP16-2021-01 (319930) and PROFAPI 2022 (PRO_A2_019) projects. K.A.P (CVU:227919) received financial support from CONACyT and is a current holder of a fellowship from the Fulbright García-Robles foundation.