Preliminary Bioinformatics Analysis Of Changes In Bat Cell Transcriptome After Interferon Stimulation

Interferon response is an important part of antiviral response in mammals.When mammalian cells are stimulated by interferon,the expression pattern of many genes will change.People have been long interested in the immune system of bats(a common name of chiropteran mammals),because bats are able to carry many viruses without getting sick.Previous studies have revealed a number of characteristics of interferon response in bats,however there are little studies on what interferon responses are common in different bats.In this thesis,we used published transcriptome data sequenced from two species of bats(representatives of both suborders of the order Chiroptera,respectively),and four species of other mammals(human,dog,rat,pig)to identify similarities of interferon response of all species examined and the features of bats' interferon responses in both gene expression and transcript usage levels.Specifically,a given gene induced by an interferon response is called an interferonstimulated gene(ISG).ISGs are the most extensively studied genes in interferon response and considered to play an important role in mammal antiviral response.In this thesis,we used published transcriptome data for our purposes of analysis.First,we screened ISGs of six mammals and found there were a huge difference between interferon responses of different species in number and expression level of ISGs.This difference is also available between two bat species,suggesting that the interferon response varies widely even among different bat species.Second,we screened core ISGs that are expressed differentially in all six mammals;our enrichment analysis confirmed that these genes mainly exist in the pathways related to antiviral and interferon responses.Third,we screened the features that are charaterized by two bats but have not been found in interferon responses of other mammals.We found that half of the bats-specific ISGs are associated with down-regulation of inflammatory response and the result is similar to what has been found in other studies about bats' immune system.The reason why bats can carry many viruses without getting sick is because they can effectively control the level of inflammation,thereby avoiding damage to its own tissues.At the same time,the process of ubiquitination showed unique enrichment characteristics in bats.The enrichment level of polyubiquitination is significantly higher than deubiquitination in rat and pig's interferon responses and even there are no significant enrichments of deubiquitination in human and dog's interferon responses,but the enrichment level of deubiquitination is significantly higher than polybibiquitination in two bats.We speculate that anti-inflammatory and protein ubiquitination may play an important role in shaping the unique immune system of bats.In addition to ISGs,genes with transcription expression changes(Transcript differential expression genes,TDGs)during interferon response from different species were also investigated.We found that the number of TDGs is significantly more than ISGs,indicating that interferon response has wider influence than that shown by ISGs screening.We screened core TDGs that have differentially expressed transcripts in all six mammals and remove some TDGs because they are considered to be core ISGs.The remaining TDGs were enriched in biological process named antigen presentation,indicating that the regulation of antigen presentation tends to rely on transcript usage change rather than changes of gene expression levels.In addition to core TDGs,some TDGs have unique expression characteristics in bats,including bat-specific TDGs(b TDGs),non-bat TDGs(nb TDGs)and TDGs that have up-regulated transcripts and down-regulated transcripts simultaneously.Through enrichment analysis and searching relevant literature,we found that most of nb TDGs are related to inflammation.This result suggests that in addition to the expression of a large number of anti-inflammatory proteins,there are also some pro-inflammatory factors that are uniquely unresponsive in bats.In addition,TDGs have unique expression characteristics in bats enriched in processes associated with p53 signaling pathway,wnt signaling pathway,and regulating membrane protein localization and methylation.These results suggest that bats have a number of features in interferon response that we have not yet identified previously,which may play an important role in shaping their unique immune systems.Though preliminary bioinformatics analysis of bat cell transcriptome after interferon stimulation,we found that there is a huge difference but some common features in interferon responses between two bats.One of the most significant charateristic is the pathway associated with inflammation.Up-regulation of some anti-inflammatory factors and unresponsiveness of some pro-inflammatory factors allow bats to take a good control of inflammation.In addition,some biological processes are enriched in interferon response of bats,such as deubiquitination found in our b ISGs analysis,and some signaling pathway associated with immune response found in our bats-specific TDGs analysis.These results not only show that many biological processes have unique changes in bats' cells after interferon stimulation,but also indicate that there are numerous complex regulating mechanisms underlying bats' unique immune systems.This work not only identified some features in interferon response of bats,but also provided useful data for future studies on the bats' unique immune systems.