vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ18.343vavilov-1376Research ArticleМОЛЕКУЛЯРНЫЕ МАРКЕРЫ В ГЕНЕТИКЕ И СЕЛЕКЦИИBIOINFORMATICS AND SYSTEM BIOLOGYАНАЛИЗ ВЗАИМОДЕЙСТВИЯ ГЕНОВ НЕЙРОНАЛЬНОГО АПОПТОЗА В АССОЦИАТИВНОЙ ГЕННОЙ СЕТИ БОЛЕЗНИ ПАРКИНСОНАANALYSIS OF THE INTERACTIONS OF NEURONAL APOPTOSIS GENES IN THE ASSOCIATIVE GENE NETWORK OF PARKINSON’S DISEASEЯнкинаМ. А.YankinaM. A.

Уфа

СайкО. В.SaikO. V.

Новосибирск

Novosibirsk

saik@bionet.nsc.ruДеменковП. С.DemenkovP. S.

Новосибирск

Novosibirsk

ХуснутдиноваЭ. К.KhusnutdinovaE. K.РогаевЕ. И.RogaevE. I.

Faculty of Bioengineering and Bioinformatics Lomonosov MSU.

Novosibirsk, Moscow, Worcester

ЛаврикИ. Н.LavrikI. N.

Novosibirsk, Magdeburg

ИванисенкоВ. А.IvanisenkoV. А.

Новосибирск

Novosibirsk

Институт биохимии и генетики Уфимского научного центра Российской академии наукРоссияInstitute of Biochemistry and Genetics, Ufa Research Centre RASRussian FederationФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияInstitute of Cytology and Genetics SB RASRussian FederationИнститут биохимии и генетики Уфимского научного центра Российской академии наук; Башкирский государственный университетРоссияInstitute of Biochemistry and Genetics, Ufa Research Centre RAS; Bashkir State UniversityRussian FederationФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Медицинская школа Массачусетского университета в Вустере; Институт общей генетики Российской академии наук; Московский государственный университет им. М.В. ЛомоносоваСоединённые Штаты АмерикиInstitute of Cytology and Genetics SB RAS; University of Massachusetts Medical School; Institute of General Genetics RAS; Lomonosov Moscow State UniversityUnited StatesФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Магдебургский университет им. Отто фон ГерикеГерманияInstitute of Cytology and Genetics SB RAS; Otto von Guericke UniversityGermany201822032018221153160Copyright © Янкина М.А., Сайк О.В., Деменков П.С., Хуснутдинова Э.К., Рогаев Е.И., Лаврик И.Н., Иванисенко В.А., 20182018Янкина М.А., Сайк О.В., Деменков П.С., Хуснутдинова Э.К., Рогаев Е.И., Лаврик И.Н., Иванисенко В.А.Yankina M.A., Saik O.V., Demenkov P.S., Khusnutdinova E.K., Rogaev E.I., Lavrik I.N., Ivanisenko V.А.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/1376

В мире болезнью Паркинсона (БП) страдают 7–10 млн человек, в России – около 210 тыс. человек. Эта болезнь сопровождается дегенерацией дофаминергических нейронов, в связи с чем нейрональный апоптоз рассматривается как важнейший фактор данного заболевания. Одним из ключевых подходов в системной биологии служит анализ генных сетей. Ранее нами была разработана система ANDSystem, предназначенная для автоматического извлечения знаний из научных публикаций и реконструкции на этой основе ассоциативных генных сетей, описывающих молекулярно-генетические механизмы биологических процессов в норме и при патологии. Целью работы было применение системы ANDSystem для приоритизации генов нейронального апоптоза, характеризующей их вовлеченность в патологические механизмы, с учетом структуры ассоциативной генной сети БП. Анализ центральности генов нейронального апоптоза, ассоциированных с БП, по данным ANDSystem, в ассоциативной генной сети БП показал, что среднее значение их центральностей по степени, близости и посредничеству статистически значимо превышает таковое, рассчитанное по всем вершинам сети БП. Среди генов, обладающих наибольшими показателями центральности, оказались APOE, CASP3 и GAPDH, играющие важную роль в нейрональном апоптозе. Приоритизация генов нейронального апоптоза, для которых в системе ANDSystem не было данных об их ассоциации с БП, проводилась с использованием стандартных методов (Endeavor и ToppGene), а также критериев центральности и специфичности их взаимодействий с ас­социативной генной сетью БП. Показано, что среди генов, обладающих наивысшим приоритетом (рассматривались 50, 70, 100 наиболее приоритетных), преимущественно представлены гены, вовлеченные в положительную и отрицательную регуляцию нейронального апоптоза, сигнальные пути MAPK и Eph-рецепторов и др., в частности TP53, JUN, BCL2, PIK3CA и APP.

Parkinson’s disease (PD) affects an estimated 7–10 million people worldwide and 210000 people in Russia. PD is accompanied by degeneration of dopaminergic neurons and because of that neuronal apoptosis is an important factor in this disease. Analysis of gene networks is one of the key approaches in systems biology. We previously developed the ANDSystem tool, designed to automatically extract knowledge from scientific publications and reconstruct on this basis associative gene networks describing the molecular genetic mechanisms of biological processes. The aim of this work was prioritization of neuronal apoptosis genes by their involvement in PD pathogenesis, taking into account the structure of the PD associative gene network using ANDSystem. Analysis of the centrality of neuronal apoptosis genes, associated with PD, revealed that mean values of degree, closeness and betweenness centralities statistically significantly exceed such values of all nodes of the PD network. The APOE, CASP3 and GAPDH genes involved in neuronal apoptosis were among the most central genes. Prioritization of neuronal apoptosis genes for which there was no data in ANDSystem on their associations with PD was performed using standard methods (Endeavor and ToppGene) and the criteria of centrality and specificity of genes interactions with the PD gene network. Analysis revealed that genes involved in such processes as positive and negative regulation of neu ronal apoptosis, MAPK and ephrin receptor signaling pathways, are mainly represented among candidate genes with the highest priority (top 50, 70, 100 genes were considered). In particular, TP53, JUN, BCL2, PIK3CA and APP were among candidate genes with the highest priority.

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