vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJGB-23-85vavilov-3972Research ArticleКОМПЬЮТЕРНАЯ ГЕНОМИКАCOMPUTATIONAL GENOMICSHuman_SNP_TATAdb – база данных о SNP, статистически достоверно изменяющих сродство ТАТА-связывающего белка к промоторам генов человека: полногеномный анализ и вариантыHuman_SNP_TATAdb: a database of SNPs that statistically significantly change the affinity of the TATA-binding protein to human gene promoters: genome-wide analysis and use casesФилоновС. В.FilonovS. V.

Новосибирск

Novosibirsk

https://orcid.org/0000-0001-9132-7997ПодколодныйН. Л.PodkolodnyyN. L.

Новосибирск

Novosibirsk

pnl@bionet.nsc.ruhttps://orcid.org/0000-0003-3247-0114ПодколоднаяО. А.PodkolodnayaO. A.

Новосибирск

Novosibirsk

ТвердохлебН. Н.TverdokhlebN. N.

Новосибирск

Novosibirsk

https://orcid.org/0000-0003-2715-9612ПономаренкоП. М.PonomarenkoP. M.

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Novosibirsk

https://orcid.org/0000-0003-4795-0954РассказовД. А.RasskazovD. A.

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Novosibirsk

https://orcid.org/0000-0003-4359-6089БогомоловА. Г.BogomolovA. G.

Новосибирск

Novosibirsk

https://orcid.org/0000-0003-1663-318XПономаренкоМ. П.PonomarenkoM. P.

Новосибирск

Novosibirsk

Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Новосибирский национальный исследовательский государственный университетРоссияInstitute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences; Novosibirsk State UniversityRussian FederationФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Институт вычислительной математики и математической геофизики Сибирского отделения Российской академии наук, НовосибирскРоссияInstitute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences; Institute of Computational Mathematics and Mathematical Geophysics, Siberian Branch of the Russian Academy of SciencesRussian FederationФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияInstitute of Cytology and Genetics, Siberian Branch of the Russian Academy of SciencesRussian Federation202311122023277728736Copyright © Филонов С.В., Подколодный Н.Л., Подколодная О.А., Твердохлеб Н.Н., Пономаренко П.М., Рассказов Д.А., Богомолов А.Г., Пономаренко М.П., 20232023Филонов С.В., Подколодный Н.Л., Подколодная О.А., Твердохлеб Н.Н., Пономаренко П.М., Рассказов Д.А., Богомолов А.Г., Пономаренко М.П.Filonov S.V., Podkolodnyy N.L., Podkolodnaya O.A., Tverdokhleb N.N., Ponomarenko P.M., Rasskazov D.A., Bogomolov A.G., Ponomarenko M.P.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/3972

Ранее было показано, что уровень экспрессии генов человека положительно коррелирует с аффинностью ТВР к промоторам этих генов. В свою очередь, однонуклеотидные полиморфизмы (SNP) в промоторах генов человека могут влиять на аффинность белка TBP к ДНК и, как следствие, на экспрессию генов. В ИЦиГ СО РАН разработан метод предсказания аффинности TBP к промоторам генов на основе трехшагового механизма связывания, включающего скольжение ТВР по ДНК, остановку ТВР в месте связывания, фиксацию комплекса ТВР–промотор за счет изгиба спирали ДНК. Метод показал высокую корреляцию теоретических предсказаний с измеренными значениями при многократной экспериментальной проверке независимыми группами исследователей. На основе этой модели в ИЦиГ СО РАН ранее были разработаны веб-сервисы SNP_TATA_Z-tester и SNP_TATA_Comparator, позволяющие вычислять статистическую оценку вызванного SNP изменения аффинности связывания TBP с промотором гена человека и прогнозировать изменение экспрессии, которые могут быть связаны с генетической предрасположенностью к заболеваниям или фенотипическими особенностями организма. В настоящей работе проведена интеграция в единой базе данных информации об однонуклеотидных полиморфизмах в промоторах генов человека, полученной путем автоматической экстракции из различных гетерогенных источников данных, а также результатов оценки аффинности TBP к промотору с использованием трехшаговой модели связывания и оценки их влияния на экспрессию генов для промоторов дикого типа и промоторов с однонуклеотидным полиморфизмом. Показана возможность использования базы данных Human_SNP_TATAdb для аннотации и выявления кандидатных SNP-маркеров заболеваний. Представлены результаты полногеномного анализа данных, включая особенности распределения генов по количеству транскриптов, распределение SNP, влияющих на аффинность TBP к ДНК по позициям внутри промоторов, а также закономерности, связывающие между собой аффинность TBP к промотору, специфичность сайта связывания TBP с промотором и другие характеристики промоторов. Результаты полногеномного анализа показали, что аффинность TBP к промотору и специфичность его сайта связывания статистически связаны с другими характеристиками промоторов, важными для функциональной классификации промоторов и исследования особенностей дифференциальной экспрессии генов.

It was previously shown that the expression levels of human genes positively correlate with TBP affinity for the promoters of these genes. In turn, single nucleotide polymorphisms (SNPs) in human gene promoters can affect TBP affinity for DNA and, as a consequence, gene expression. The Institute of Cytology and Genetics SB RAS (ICG) has developed a method for predicting TBP affinity for gene promoters based on a three-step binding mechanism: (1) TBP slides along DNA, (2) TBP stops at the binding site, and (3) the TBP-promoter complex is fixed due to DNA helix bending. The method showed a high correlation of theoretical predictions with measured values during repeated experimental testing by independent groups of researchers. This model served as a base for other ICG web services, SNP_TATA_Z-tester and SNP_TATA_Comparator, which make a statistical assessment of the SNP-induced change in the affinity of TBP binding to the human gene promoter and help predict changes in expression that may be associated with a genetic predisposition to diseases or phenotypic features of the organism. In this work, we integrated into a single database information about SNPs in human gene promoters obtained by automatic extraction from various heterogeneous data sources, as well as the estimates of TBP affinity for the promoter obtained using the three-step binding model and predicting their effect on gene expression for wild-type promoters and promoters with SNPs. We have shown that Human_SNP_TATAdb can be used for annotation and identification of candidate SNP markers of diseases. The results of a genome-wide data analysis are presented, including the distribution of genes with respect to the number of transcripts, the distribution of SNPs affecting TBP-DNA affinity with respect to positions within promoters, as well as patterns linking TBP affinity for the promoter, the specificity of the TBP binding site for the promoter and other characteristics of promoters. The results of the genome-wide analysis showed that the affinity of TBP for the promoter and the specificity of its binding site are statistically related to other characteristics of promoters important for the functional classification of promoters and the study of the features of differential gene expression.

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The authors declare that there are no conflicts of interest present.