Analysis Of The Key Gene Modules And Expression Regulatory Networks With Their Transcription Factors In Space-flown Caenorhabditis Elegans

Astronauts are inevitably exposed to the space environment during space missions.Space radiation and microgravity,as the two most important unique environmental factors in the space environment,can cause a variety of health risks to astronauts,which are considered to be the main restricted factors for long-term on-orbit and deep space exploration missions.Caenorhabditis elegans has been widely used as a model organism in space flight experiments due to its advantages of easy cultivation,small size,and high homology with humans,which provides important data sources for exploring the biological effects and their regulatory mechanisms under space environment.Deep data mining and analysis of transcriptome data in space-flown C.elegans can contribute to assessing possible health risks under spaceflight conditions and identify the key molecular targets for biomedical protection.Therefore,by using the multiple transcriptome datasets of C.elegans under different space flight conditions,this study aimed to deeply mine key gene modules,predict their transcription factors,and analyze the gene expression regulatory network between the genes in the key modules and their regulatory transcription factors.Through this study,we obtained the results as following.(1)The differentially expressed genes of C.elegans were analyzed and obtained under different space flight conditions.The results showed that 382 genes were up-regulated and5,174 genes were down-regulated under 4-day spaceflight;360 genes were up-regulated and797 genes were down-regulated under 8-day spaceflight;454 genes were up-regulated and1,330 genes were down-regulated under 10-day spaceflight;and 2,719 genes were up-regulated and 1,758 genes were down-regulated under the condition of 6-month spaceflight,respectively.Further,the common genes of these differentially expressed genes under different spaceflight conditions was analyzed,and the results showed 32 genes were significant changed in all spaceflight conditions.Through ss GSEA enrichment analysis of these genes,we obtained 6significant pathways annotated in the KEGG database,mainly including longevity regulation pathway,endoplasmic reticulum protein processing,endocytosis,etc.,and 43 biological processes annotated in the GO database,mainly including nervous system development,protein folding,lifespan and aging,defense response,response to external stimuli,cell communication,etc.Further,we performed the enrichment analysis of the up-regulated and down-regulated genes under different space flight conditions,and screened for the significant pathways and biological processes annotated in the KEGG and GO databases.The results showed that 7 key gene modules,including defense response module,response to misfolded protein module,autophagy module,DNA repair module,longevity regulating module,reproduction module and embryo development module,were obtained under these spaceflights.(2)By using the methods of cluster and protein interaction network analysis,we analyze the expression patterns and screen the key genes with high connectivity in these key gene modules.The results showed that the gene expression in these key gene modules were well clustered under different space flight conditions,which indicated that these genes had obvious time dependence.For example,we found that with the extension of spaceflight time,the gene expression in DNA repair module showed a significant trend of increase,which may be due to the accumulation of DNA damage induced by space flight.In addition,we also found that the key genes of the defense response module were lys-1 and sta-1;the key genes of the module of the response to misfolded protein were F44E5.4,hsp-16.41,hsp-16.48,hsp-16.11 and hsp-70;the key genes of the autophagy module were C35E7.5,vet-6,sepa-1,sdz-30 and bec-1;the key genes of the DNA repair module were F10C2.4,pcn-1,crn-1,pole-1 and rad-51;the key genes of the longevity regulating module were hsp-70 and daf-2;the key genes of the reproduction module were cyb-2.2,tra-1 and vab-3;the key genes of the embryo development module were rad-51 and ima-2,respectively.The transcription factors that regulate gene expression of key modules were further predicted.The results show that transcription factors such as alg-1,pha-4,blmp-1,csr-1,dpl-1,and skn-1 may be involved in the regulation of gene expression in multiple key modules.Based on all these results,we established the gene expression regulatory network between the transcription factors and genes associated with the key modules under different spaceflights.In conclusions,the differentially expressed genes and key gene modules were obtained in C.elegans experienced with different space flight conditions.The key gene modules were involved in defense response,response to misfolded protein,autophagy,DNA repair,longevity regulating,reproduction module and embryo development,respectively.Further,we screened the important functional genes in these key modules,and analyzed the expression patterns of these module genes.In addition,we also predicted the transcription factors regulated the genes expressions of these indentified modules,and obtained the corresponding expression regulatory networks.This study provides a new insight for the study of the biological effects and mechanisms in space-flown C.elegans,as well as important support for health risk assessment and biomedical protection of astronauts.