SNP analysis in COVID-19 with TRANSFAC Public, TRANSFAC Professional, and JASPAR скачать в хорошем качестве

SNP analysis in COVID-19 with TRANSFAC Public, TRANSFAC Professional, and JASPAR

When searching for transcription factors governing regulation the genes of your interest, it is of crucial importance which collection of position weight matrices (PWMs or DNA-binding models) is going to be used for the performed analysis. In this video Dr. Alexander Kel, the CSO of geneXplain GmbH, analyzes an important SNP in the LZTFL1 gene which was identified in a recent genome wide association study as one of the most important genetically predisposed risk factors of COVID-19 infection. Dr. Kel analyzes this SNP by searching for transcription factors which binding sites have changed because of the change of the nucleotides in this SNP. The search is performed three times using different libraries of PWMs from three different databases: (1) TRANSFAC Professional (2) TRANSFAC Public (3) JASPAR. Same cutoff values are used for all three runs. When performing the analysis with the library from TRANSFAC Professional database, it was identified that VDR (vitamin D receptor) and IRF3 transcription factors have lost or gained their sites due to the nucleotide changes in the studied SNP. A recent paper has shown that interferon regulation is inhibited by many proteins from coronavirus, especially it was shown that IRF3 transcription factor is also inhibited, which plays an key role in regulation of interferon genes. In addition to that, recent papers have shown that vitamin D is highly involved in the coronavirus severity. This makes our finding supportive to these recent data hypothesizing that the change of binding sites of VDR and IRF3 due to the SNP in LZTFL1 gene can contribute to the differences in its regulation leading to higher severity of COVID-19 disease in the individuals caring the alternative allele. When performing the same analysis with the library from TRANSFAC Public database, it appeared that there were no IRF3 or VDR sites predicted in the results. This happened because there are no IRF3 matrices and no VDR matrices in TRANSFAC Public. When performing the same analysis with the library from JASPAR database, it appeared that the gained site of the VDR transcription factor was successfully identified, but the IRF3 sites were not found. This happed because in the JASPAR database there was only one IRF3 matrix, not well matching the site in studied region, while TRANSFAC Professional had 11 IRF3 matrices, one of which was built by our team by using information from binding sites from SARS coronavirus infections. So that's why, probably, this matrix worked in the case of the COVID-19 related SNP.