Mechanism of CAV and CAVIN Family Genes in Acute Lung Injury based on DeepGENE

Page: [72 - 80] Pages: 9

  • * (Excluding Mailing and Handling)

Abstract

Background: The fatality rate of acute lung injury (ALI) is as high as 40% to 60%. Although various factors, such as sepsis, trauma, pneumonia, burns, blood transfusion, cardiopulmonary bypass, and pancreatitis, can induce ALI, patients with these risk factors will eventually develop ALI. The rate of developing ALI is not high, and the outcomes of ALI patients vary, indicating that it is related to genetic differences between individuals. In a previous study, we found multiple functions of cavin-2 in lung function. In addition, many other studies have revealed that CAV1 is a critical regulator of lung injury. Due to the strong relationship between cavin-2 and CAV1, we suspect that cavin-2 is also associated with ALI. Furthermore, we are curious about the role of the CAV family and cavin family genes in ALI.

Methods: To reveal the mechanism of CAV and CAVIN family genes in ALI, we propose DeepGENE to predict whether CAV and CAVIN family genes are associated with ALI. This method constructs a gene interaction network and extracts gene expression in 84 tissues. We divided these features into two groups and used two network encoders to encode and learn the features.

Results: Compared with DNN, GBDT, RF and KNN, the AUC of DeepGENE increased by 7.89%, 16.84%, 20.19% and 32.01%, respectively. The AUPR scores increased by 8.05%, 15.58%, 22.56% and 23.34%. DeepGENE shows that CAVIN-1, CAVIN-2, CAVIN-3 and CAV2 are related to ALI.

Conclusion: DeepGENE is a reliable method for identifying acute lung injury-related genes. Multiple CAV and CAVIN family genes are associated with acute lung injury-related genes through multiple pathways and gene functions.

Keywords: CAV family genes, CAVIN family genes, acute lung injury, deep learning, gene expression, gene network.

Graphical Abstract

[1]
Christiani DC. Vaping-induced acute lung injury. Mass Medical Soc 2020; 382: 960-2.
[2]
Fujishima S, Gando S, Daizoh S, et al. Infection site is predictive of outcome in acute lung injury associated with severe sepsis and septic shock. Respirology 2016; 21(5): 898-904.
[http://dx.doi.org/10.1111/resp.12769] [PMID: 27028604]
[3]
Rajasekaran S, Pattarayan D, Rajaguru P, Sudhakar Gandhi PS, Thimmulappa RK. MicroRNA regulation of acute lung injury and acute respiratory distress syndrome. J Cell Physiol 2016; 231(10): 2097-106.
[http://dx.doi.org/10.1002/jcp.25316] [PMID: 26790856]
[4]
Cui L, Zheng D, Lee YH, et al. Metabolomics investigation reveals metabolite mediators associated with acute lung injury and repair in a murine model of influenza pneumonia. Sci Rep 2016; 6(1): 26076.
[http://dx.doi.org/10.1038/srep26076] [PMID: 27188343]
[5]
Komiya K, Akaba T, Kozaki Y, Kadota J, Rubin BK. A systematic review of diagnostic methods to differentiate acute lung injury/acute respiratory distress syndrome from cardiogenic pulmonary edema. Crit Care 2017; 21(1): 228.
[http://dx.doi.org/10.1186/s13054-017-1809-8] [PMID: 28841896]
[6]
Cao Y, Lyu Y, Tang J, Li Y. MicroRNAs: Novel regulatory molecules in acute lung injury/acute respiratory distress syndrome. Biomed Rep 2016; 4(5): 523-7.
[http://dx.doi.org/10.3892/br.2016.620] [PMID: 27123242]
[7]
Semple JW, Rebetz J, Kapur R. Transfusion-associated circulatory overload and transfusion-related acute lung injury. Blood 2019; 133(17): 1840-53.
[http://dx.doi.org/10.1182/blood-2018-10-860809] [PMID: 30808638]
[8]
Lo Coco G, Melchiori F, Oieni V, et al. Group treatment for substance use disorder in adults: A systematic review and meta-analysis of randomized-controlled trials. J Subst Abuse Treat 2019; 99: 104-16.
[http://dx.doi.org/10.1016/j.jsat.2019.01.016] [PMID: 30797382]
[9]
Zhao T, Hu Y, Zang T, Cheng L. MRTFB regulates the expression of NOMO1 in colon. Proc Natl Acad Sci USA 2020; 117(14): 7568-9.
[http://dx.doi.org/10.1073/pnas.2000499117] [PMID: 32184333]
[10]
Zhao T, Lyu S, Lu G, et al. SC2disease: A manually curated database of single-cell transcriptome for human diseases. Nucleic Acids Res 2021; 49(D1): D1413-9.
[http://dx.doi.org/10.1093/nar/gkaa838] [PMID: 33010177]
[11]
Cheng N, Chen C, Li C, Huang J. Inferring cell-type-specific genes of lung cancer based on deep learning. Curr Gene Ther 2022.
[http://dx.doi.org/10.2174/1566523222666220324110914]
[12]
Zhao T, Liu J, Zeng X, et al. Prediction and collection of protein-metabolite interactions. Brief Bioinform 2021; 22(5): bbab014.
[http://dx.doi.org/10.1093/bib/bbab014] [PMID: 33554247]
[13]
Reghunathan R, Jayapal M, Hsu LY, et al. Expression profile of immune response genes in patients with Severe Acute Respiratory Syndrome. BMC Immunol 2005; 6(1): 2.
[http://dx.doi.org/10.1186/1471-2172-6-2] [PMID: 15655079]
[14]
Yu Y, Jiang P, Sun P, Su N, Lin F. Pulmonary coagulation and fibrinolysis abnormalities that favor fibrin deposition in the lungs of mouse antibody-mediated transfusion-related acute lung injury. Mol Med Rep 2021; 24(2): 601.
[http://dx.doi.org/10.3892/mmr.2021.12239] [PMID: 34165170]
[15]
Nagase T, Uozumi N, Ishii S, et al. Acute lung injury by sepsis and acid aspiration: A key role for cytosolic phospholipase A2. Nat Immunol 2000; 1(1): 42-6.
[http://dx.doi.org/10.1038/76897] [PMID: 10881173]
[16]
Gong MN, Zhou W, Williams PL, et al. −308GA and TNFB polymorphisms in acute respiratory distress syndrome. Eur Respir J 2005; 26(3): 382-9.
[http://dx.doi.org/10.1183/09031936.05.00000505] [PMID: 16135717]
[17]
Flores C, Ma SF, Maresso K, Wade MS, Villar J, Garcia JGN. IL6 gene-wide haplotype is associated with susceptibility to acute lung injury. Transl Res 2008; 152(1): 11-7.
[http://dx.doi.org/10.1016/j.trsl.2008.05.006] [PMID: 18593632]
[18]
Hildebrand F, Stuhrmann M, van Griensven M, et al. Association of IL-8-251A/T polymorphism with incidence of Acute Respiratory Distress Syndrome (ARDS) and IL-8 synthesis after multiple trauma. Cytokine 2007; 37(3): 192-9.
[http://dx.doi.org/10.1016/j.cyto.2007.03.008] [PMID: 17498967]
[19]
Gong MN, Thompson BT, Williams PL, et al. Interleukin-10 polymorphism in position -1082 and acute respiratory distress syndrome. Eur Respir J 2006; 27(4): 674-81.
[http://dx.doi.org/10.1183/09031936.06.00046405] [PMID: 16585075]
[20]
Schroeder O, Schulte KM, Schroeder J, Ekkernkamp A, Laun RA. The -1082 interleukin-10 polymorphism is associated with acute respiratory failure after major trauma: A prospective cohort study. Surgery 2008; 143(2): 233-42.
[http://dx.doi.org/10.1016/j.surg.2007.07.040] [PMID: 18242340]
[21]
Youya Wang, Zhifeng Ning, Xuefeng Zhou. Neuregulin1 acts as a suppressor in human lung adenocarcinoma via AKT and ERK1/2 pathway. J Thorac Dis 2018; 10(6): 3166-79.
[http://dx.doi.org/10.21037/jtd.2018.05.175]
[22]
Piñero J, Bravo À, Queralt-Rosinach N, et al. DisGeNET: A comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res 2016; gkw943.
[PMID: 27924018]
[23]
Wu C, Orozco C, Boyer J, et al. BioGPS: An extensible and customizable portal for querying and organizing gene annotation resources. Genome Biol 2009; 10(11): R130.
[http://dx.doi.org/10.1186/gb-2009-10-11-r130] [PMID: 19919682]
[24]
Kreisel D, Sugimoto S, Tietjens J, et al. Bcl3 prevents acute inflammatory lung injury in mice by restraining emergency granulopoiesis. J Clin Invest 2011; 121(1): 265-76.
[http://dx.doi.org/10.1172/JCI42596] [PMID: 21157041]
[25]
Price WA, Moats-Staats BM, Stiles AD. Pro- and anti-inflammatory cytokines regulate insulin-like growth factor binding protein production by fetal rat lung fibroblasts. Am J Respir Cell Mol Biol 2002; 26(3): 283-9.
[http://dx.doi.org/10.1165/ajrcmb.26.3.4601] [PMID: 11867336]
[26]
Li C, Huang J, Tang H, Liu B, Zhou X. Revealing cavin-2 gene function in lung based on multi-omics data analysis method. Front Cell Dev Biol 2022; 9: 827108.
[http://dx.doi.org/10.3389/fcell.2021.827108] [PMID: 35174175]
[27]
Szklarczyk D, Gable AL, Lyon D, et al. STRING v11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res 2019; 47(D1): D607-13.
[http://dx.doi.org/10.1093/nar/gky1131] [PMID: 30476243]
[28]
Wang W, Chen N, Ren D, et al. Enhancing extracellular adenosine levels restores barrier function in acute lung injury through expression of focal adhesion proteins. Front Mol Biosci 2021; 8: 636678.
[http://dx.doi.org/10.3389/fmolb.2021.636678] [PMID: 33778007]
[29]
Patel A, Sangle GV, Trivedi J, et al. Levonadifloxacin, a novel benzoquinolizine fluoroquinolone, modulates lipopolysaccharide-induced inflammatory responses in human whole-blood assay and murine acute lung injury model. Antimicrob Agents Chemother 2020; 64(5): e00084-20.
[http://dx.doi.org/10.1128/AAC.00084-20] [PMID: 32152077]