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. 2021 Jun 22;12:610774. doi: 10.3389/fgene.2021.610774

FIGURE 1.

FIGURE 1

The result produced by SNP_TATA_Comparator (Ponomarenko et al., 2015) in the case of a clinically proven SNP marker (rs2276109) of an asthma risk reduction due to MMP12 downregulation (Hunninghake et al., 2009), which is associated with a reduced risk of rheumatoid arthritis, RA (Liu et al., 2004). (A) The UCSC Genome Browser (Haeussler et al., 2015) visualizes a 70-bp promoter (double-headed dash-and-dot arrow) of a given human gene (here: MMP12, row 2, left column), where there are a TBP-binding site (TBP-site; framed, □) and SNPs retrieved from dbSNP (Day, 2010); their IDs constitute the left-hand column. (B) The Bioperl toolkit (Stajich et al., 2002). (C) The Ensembl database (Zerbino et al., 2015). (D) The current build (No. 151) of the dbSNP database describes the SNP under study (rs2276109 in this example). (E) Our prediction of MMP12 downregulation (textbox “Result”: row 3) caused by SNP rs2276109 (circled) by means of its both alleles (i.e., ancestral and minor ones as input data within two textboxes “Basic sequence” and “Editable sequence,” respectively). Double-headed open arrows (⇔) depict how SNP_TATA_Comparator retrieved the ancestral DNA sequence of the human MMP12 promoter from the Ensembl database (Zerbino et al., 2015) using the Bioperl toolkit (Stajich et al., 2002). (F) Our bioinformatics model of the TBP-promoter binding via three steps, as follows: (1) TBP sliding along DNA ↔ (2) TBP retarded by the TBP-site ↔ the TBP-promoter complex is fixed due to the bending of the DNA double helix at right angles (Ponomarenko et al., 2008). This model is based on the standard bioinformatical package of R (Waardenberg et al., 2015), as described in Supplementary File 1: Supplementary Methods. Solid arrows: data flows, when one predicts the manifestation of a given SNP using SNP_TATA_Comparator; dashed arrow: the SNP in this example (rs2276109); dotted arrows: two more SNPs, rs572527200 and rs1401366377 (Figure 3A), which correspond to either underexpression or overexpression of MMP12, respectively, as predicted in this work.