How to Use SNP_TATA_Comparator to Find a Significant Change in Gene Expression Caused by the Regulatory SNP of This Gene’s Promoter via a Change in Affinity of the TATA-Binding Protein for This Promoter

Пономаренко, М. П.; Рассказов, Д. А.; Arkova, Olga; Пономаренко, П. М.; Суслов, В. В.; Савинкова, Л. К.; Колчанов, Н. А.

doi:10.1155/2015/359835

Cited by 32 publications

(142 citation statements)

References 131 publications

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“…For each proximal 90 bp DNA sequence { s −90 ⋯ s −1 } of a given gene promoter (where s i ∈ { a , c , g , t }; s 0 is the transcription start site), our Web service SNP_TATA_Comparator [35] calculates the maximal value of −ln⁡( K D ) ± δ of the estimate of TBP's binding affinity for the 26 bp window { s i −13 ⋯ s i ⋯ s i +12 } [116, 117] (where −70 ≤ i ≤ −20 in both DNA strands; K D is the equilibrium dissociation constant of the TBP-DNA complex, expressed in moles per liter; M), as follows:

\begin{matrix} T∞5 \\ \ln (K_{D}) = 10.9 - 0.2 \{\ln (K_{1} ([T A]; μ)) + \ln (K_{2} ({P W M}_{B u c h e r})) + \ln (K_{3} ([W R]; [T V]))\}; \end{matrix}

\begin{matrix} δ = \frac{1}{78} \\ \cdot {false\sum}_{φ \in ({}|, a, t, g,)} \end{matrix}

…”

Section: Methodsmentioning

confidence: 99%

“…Our Web service SNP_TATA_Comparator [35] compares them using Fisher's Z -score [124]:

\begin{matrix} T1 \\ Z = \frac{|\ln (K_{D}^{(m u t)} / K_{D}^{(w t)})|}{\sqrt{δ_{(|, normalm normalu normalt)}^{normal2} + δ_{(|, normalw normalt)}^{normal2}}} . \end{matrix}

…”

Section: Methodsmentioning

confidence: 99%

“…Two cases, “ K D (mut) < K D (wt) ” and “ K D (mut) > K D (wt) ,” correspond, respectively, to overexpression and underexpression of the gene under study [125]. For more details, see our previous article [35]. …”

Section: Methodsmentioning

confidence: 99%

“…wt, ancestral allele; mut, minor allele; K D , an estimate [35] of the dissociation constant ( K D ) of the TBP-DNA complex in vitro [91]; Δ, a gene expression change in comparison with the norm (=): overexpression (↑) and underexpression (↓); Z , Z -score; α = 1 − p , significance (where p is a probability rate of acceptance of H 0 hypothesis “ K D (mut) ≠ K D (wt) ”; see Figure 1); TF, transcription factor; EMSA, electrophoretic mobility shift assay.…”

Section: Figurementioning

confidence: 99%

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Candidate SNP Markers of Chronopathologies Are Predicted by a Significant Change in the Affinity of TATA-Binding Protein for Human Gene Promoters

Пономаренко

Рассказов

Суслов

et al. 2016

BioMed Research International

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Variations in human genome (e.g., single nucleotide polymorphisms, SNPs) may be associated with hereditary diseases, their complications, comorbidities, and drug responses. Using Web service SNP_TATA_Comparator presented in our previous paper, here we analyzed immediate surroundings of known SNP markers of diseases and identified several candidate SNP markers that can significantly change the affinity of TATA-binding protein for human gene promoters, with circadian consequences. For example, rs572527200 may be related to asthma, where symptoms are circadian (worse at night), and rs367732974 may be associated with heart attacks that are characterized by a circadian preference (early morning). By the same method, we analyzed the 90 bp proximal promoter region of each protein-coding transcript of each human gene of the circadian clock core. This analysis yielded 53 candidate SNP markers, such as rs181985043 (susceptibility to acute Q fever in male patients), rs192518038 (higher risk of a heart attack in patients with diabetes), and rs374778785 (emphysema and lung cancer in smokers). If they are properly validated according to clinical standards, these candidate SNP markers may turn out to be useful for physicians (to select optimal treatment for each patient) and for the general population (to choose a lifestyle preventing possible circadian complications of diseases).

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\begin{matrix} T∞5 \\ \ln (K_{D}) = 10.9 - 0.2 \{\ln (K_{1} ([T A]; μ)) + \ln (K_{2} ({P W M}_{B u c h e r})) + \ln (K_{3} ([W R]; [T V]))\}; \end{matrix}

\begin{matrix} δ = \frac{1}{78} \\ \cdot {false\sum}_{φ \in ({}|, a, t, g,)} \end{matrix}

…”

Section: Methodsmentioning

confidence: 99%

“…Our Web service SNP_TATA_Comparator [35] compares them using Fisher's Z -score [124]:

\begin{matrix} T1 \\ Z = \frac{|\ln (K_{D}^{(m u t)} / K_{D}^{(w t)})|}{\sqrt{δ_{(|, normalm normalu normalt)}^{normal2} + δ_{(|, normalw normalt)}^{normal2}}} . \end{matrix}

…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

See 2 more Smart Citations

Candidate SNP Markers of Chronopathologies Are Predicted by a Significant Change in the Affinity of TATA-Binding Protein for Human Gene Promoters

Пономаренко

Рассказов

Суслов

et al. 2016

BioMed Research International

Self Cite

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“…Earlier, we developed the public Web service SNP_TATA_Comparator (http://beehive.bionet.nsc.ru/cgi-bin/mgs/tatascan/start.pl) [51, 52] for estimation of the statistical significance (Fisher’s Z-score) of the difference between ancestral and minor SNP variants of a given TBP-binding site in terms of the expression change of the gene whose promoter contains this site [53]. This estimation was explored in detail by our experiments in vitro under both equilibrium [54] and nonequilibrium [55] conditions of the electrophoretic mobility shift assay (EMSA).…”

Section: Introductionmentioning

confidence: 99%

Candidate SNP markers of aggressiveness-related complications and comorbidities of genetic diseases are predicted by a significant change in the affinity of TATA-binding protein for human gene promoters

et al. 2016

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BackgroundAggressiveness in humans is a hereditary behavioral trait that mobilizes all systems of the body—first of all, the nervous and endocrine systems, and then the respiratory, vascular, muscular, and others—e.g., for the defense of oneself, children, family, shelter, territory, and other possessions as well as personal interests. The level of aggressiveness of a person determines many other characteristics of quality of life and lifespan, acting as a stress factor. Aggressive behavior depends on many parameters such as age, gender, diseases and treatment, diet, and environmental conditions. Among them, genetic factors are believed to be the main parameters that are well-studied at the factual level, but in actuality, genome-wide studies of aggressive behavior appeared relatively recently. One of the biggest projects of the modern science—1000 Genomes—involves identification of single nucleotide polymorphisms (SNPs), i.e., differences of individual genomes from the reference genome. SNPs can be associated with hereditary diseases, their complications, comorbidities, and responses to stress or a drug. Clinical comparisons between cohorts of patients and healthy volunteers (as a control) allow for identifying SNPs whose allele frequencies significantly separate them from one another as markers of the above conditions. Computer-based preliminary analysis of millions of SNPs detected by the 1000 Genomes project can accelerate clinical search for SNP markers due to preliminary whole-genome search for the most meaningful candidate SNP markers and discarding of neutral and poorly substantiated SNPs.ResultsHere, we combine two computer-based search methods for SNPs (that alter gene expression) {i} Web service SNP_TATA_Comparator (DNA sequence analysis) and {ii} PubMed-based manual search for articles on aggressiveness using heuristic keywords. Near the known binding sites for TATA-binding protein (TBP) in human gene promoters, we found aggressiveness-related candidate SNP markers, including rs1143627 (associated with higher aggressiveness in patients undergoing cytokine immunotherapy), rs544850971 (higher aggressiveness in old women taking lipid-lowering medication), and rs10895068 (childhood aggressiveness-related obesity in adolescence with cardiovascular complications in adulthood).ConclusionsAfter validation of these candidate markers by clinical protocols, these SNPs may become useful for physicians (may help to improve treatment of patients) and for the general population (a lifestyle choice preventing aggressiveness-related complications).Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3353-3) contains supplementary material, which is available to authorized users.

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Rheumatoid arthritis: pathogenesis and therapeutic advances

Gao,

Zhang,

Liu

2024

MedComm

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Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the unresolved synovial inflammation for tissues‐destructive consequence, which remains one of significant causes of disability and labor loss, affecting about 0.2–1% global population. Although treatments with disease‐modifying antirheumatic drugs (DMARDs) are effective to control inflammation and decrease bone destruction, the overall remission rates of RA still stay at a low level. Therefore, uncovering the pathogenesis of RA and expediting clinical transformation are imminently in need. Here, we summarize the immunological basis, inflammatory pathways, genetic and epigenetic alterations, and metabolic disorders in RA, with highlights on the abnormality of immune cells atlas, epigenetics, and immunometabolism. Besides an overview of first‐line medications including conventional DMARDs, biologics, and small molecule agents, we discuss in depth promising targeted therapies under clinical or preclinical trials, especially epigenetic and metabolic regulators. Additionally, prospects on precision medicine based on synovial biopsy or RNA‐sequencing and cell therapies of mesenchymal stem cells or chimeric antigen receptor T‐cell are also looked forward. The advancements of pathogenesis and innovations of therapies in RA accelerates the progress of RA treatments.

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How to Use SNP_TATA_Comparator to Find a Significant Change in Gene Expression Caused by the Regulatory SNP of This Gene’s Promoter via a Change in Affinity of the TATA-Binding Protein for This Promoter

Cited by 32 publications

References 131 publications

Candidate SNP Markers of Chronopathologies Are Predicted by a Significant Change in the Affinity of TATA-Binding Protein for Human Gene Promoters

Candidate SNP Markers of Chronopathologies Are Predicted by a Significant Change in the Affinity of TATA-Binding Protein for Human Gene Promoters

Candidate SNP markers of aggressiveness-related complications and comorbidities of genetic diseases are predicted by a significant change in the affinity of TATA-binding protein for human gene promoters

Rheumatoid arthritis: pathogenesis and therapeutic advances

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