Application of the Generecommender technology to the outcome of the paper: " Global transcriptomic changes occur in uterine fluid-derived extracellular vesicles during the endometrial window for embryo implantation"
In the cited article the authors designed three experiments to investigate the transcriptome of endometrial tissue with uterine ﬂuid-derived extracellular vesicles (UF-EVs) a promising and easily accessible possible model for receptivity test.
A different comparison was carried out:
• Differential gene expression between UF-EVs and endometrium cells.
• After taking 14 fertile women, perform a differential gene expression of UF-EVs in the receptive state (7 days after the peak of LH hormone) and UF-EVs in a non-receptive state (2 days after the peak of LH hormone) to identify the specific transcriptomic modifications in place in this status.
• Differential gene expression of women successful pregnancy vs failed pregnancy after undergoing (Assisted Reproductive Technology) ART.
After RNA isolation cDNA libraries were generated using QuantSeq 3’ mRNA-Seq Library Prep Kit and sequenced on Illumina NextSeq 500 and Illumina NovaSeq 6000 to obtain 15 million single-end reads per sample. The adapters were trimmed using Trimmomatic and the resulting reads aligned with GRCh38. RNA-seq data were normalized for different library sizes by calculating the Counts Per Million (CPM) and this measure was used to define expressed gene (at least 1 CPM in a selected number of samples based on the size of the compared groups).
The study demonstrates that there is a high correlation (r’s Pearson= 0.7) between the transcriptional profile of UF-EVs and endometrial tissue and that there is a clear distinction between UF-EVs in the receptive state vs UF-EVs in the non-receptive state (2247 genes differentially expressed).
We focused on the third comparison, successful vs failed pregnancy. Giving as input to Gene Recommender the genes with an already known correlation with female infertility available in the literature and most accredited databasesi, we found that among the 50 first recommendations, 4 were present in the list of 161 differentially expressed genes (Fisher test, pval<0.01). One of them, DUSP1, is one of the most correlated, having a Log2 fold change with and absolute value greater than 3.
[i] Input genes Facioscapulohumeral Dystrophy: [ CYP19A1 , CACNA2D2 , LHB , LIF , ARNTL , MTHFR , PAPPA , ADIPOR1 , MAPK1 , MAPK3 , PRL , SMO , NR2F2 , TP53 , ADIPOR2 , NR1I2 , LEPR , LEP , CEBPA , CEBPB , CCN2 , CYP17A1 , DHFR , ESR1 , ESR2 , AR , FSHB , NR5A2 ]