Weighted Gene CO-Expression Network Analysis Revealed Dynamic Transcriptome Alteration in Human PreimplantationEmbryonic Cells

Background: Preimplantation embryo in human is divided intoseveral stages. These stages comes with important processesaffecting next levels of embryo development. It has been revealedthat each stage of preimplantation embryo has its specifictranscriptome. As a high throughput data, a way to analyzetranscriptome is network based studied in the systems level.Weighted Gene Co-expression Network Analysis (WGCNA)is a reliable and broadly applied network analyses that usestranscriptome data to detect modules of highly correlated expressedgenes. Here, we have applied WGCNA to detect moduleof genes which are related to each stage of preimplantationembryo. We also analyzed transcription factors (TFs) relatedto each stage to see transcription regulatory alterations duringpreimplantation embryo. Additionally, by detecting coordinatesof members of significantly related modules to the stages welooked for potential common motifs in their upstream region.Materials and Methods: We collected a RNA-seq dataset(GSE۳۶۵۵۲) contains several samples for Oocyte, Zygote, ۲cell, ۴ cell, and ۸ cell. Matrix of RPKM values were processedto remove unfavorable genes to reduce noise and bias. Then,WGCNA analyses were performed using R programming andannotation of stage-related modules were considered applyingDAVID database. Parallel plot of expression values of the modulemembers were detected to check the trend of gene expressionduring preimplantation. All TFs involved in preimplantationembryo stages were detect comparing the matrix with allTFs of human. Coordinate of the module members were obtainusing genome table of UCSC database and motifs in -۱۵۰۰ regionwere analyzed by RSAT database.Results: After processing of early matrix, we prepared a matrixcontain ۱۰۸۵۰ genes. We detected several modules related toeach stages. Annotation of modules detected that transcription,cell division, and cell adhesion are main biological processesin all stages. Parallel plots showed that almost all the genesin the modules are upregulated in zygote to ۴ cell stages anddown-regulated in ۸ cell stage. Clustering of TFs by correlationgrouped them into two subclasses that are differ in expressionpattern. They grouped samples into ۳ different clusters includingzygote, oocyte and ۲ cell in a cluster, ۴ cell and ۸ cell in separateclusters, as well. TFs that control the clustered TFs werepredicted and grouped into two clearly different clusters. Themotif discovery analyses also detected some specific motifs atupstream region of the module members.Conclusion: Our analysis have detected some specific TFs andmotifs for preimplantation embryo in human. These resultsmay shed light on embryo development knowledge and may behelpful for future studies.

کلیدواژه ها:

Embryo ، RNA-Seq ، Transcription Factors ، WGCNA