A study of genes controlling carcinogenesis in a regenerative model flatworm Macrostomum lignano

Poster (download) Kitill Ustyantsev1, Valeriya Vavilova2, Mikhail Biryukov3, Eugene Berezikov41Sector of molecular-genetic mechanisms of regeneration ICG SB RAS Novosibirsk, Russia, ustyantsev@bionet.nsc.ru2Sector of molecular-genetic mechanisms of regeneration ICG SB RAS Novosibirsk, Russia, valeriya-vavilova@bionet.nsc.ru3Interinstitutional laboratory of molecular paleogenetics and paleogenomics ICG SB RAS Novosibirsk, Russia, birykov@bionet.nsc.ru4Sector of molecular-genetic mechanisms of regeneration ICG SB RAS Novosibirsk, Russia European Research Institute for the Biology of Ageing Groningen, The Netherlands, eberez@bionet.nsc.ru В Free-living flatworm Macrostomum lignano is a novel model organism that provides a genetically tractable experimental system to specifically study the interplay between regulation of regeneration and cancer. Here, we tested two chemical carcinogens (MMS and CsA) and short wavelength ultraviolet irradiation (UVC) in M. lignano in order to identify genes and molecular pathways underlying carcinogenic response in this flatworms. For the first time, sensitivity of M. lignano to hard UV was evaluated, and it was shown that the worm can easily tolerate sterilization-level doses of higher than 100 mJ/cm2. Using differential gene expression analysis based on generated RNA-Seq data, common and individual patterns of M. lignano transcriptional response to the induced carcinogenesis by the tested stimuli were determined. This allowed us to select promising candidate genes for functional studies using RNAi knock-down screens and for determination of their role in stem cells regulation under regeneration and homeostasis in M. lignano.

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Transcriptional profiling of ventral tegmental area of male mice with alternative patterns of social behaviors

Poster (download) Olga Redina1, Vladimir Babenko2, Vadim Efimov3, Dmitry Smagin4, Irina Kovalenko5, Anna Galyamina6, Natalia Kudryavtseva71Laboratory of Neuropathology Modeling, Laboratory of Evolutional Genetics, Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia, oredina@bionet.nsc.ru2Laboratory of Neuropathology Modeling, Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia, bob@bionet.nsc.ru3Laboratory of Molecular Genetic Systems Modeling, Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia, efimov@bionet.nsc.ru4Laboratory of Neuropathology Modeling, Neurogenetics of Social Behavior Sector, Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia, smagin@bionet.nsc.ru5Laboratory of Neuropathology Modeling, Neurogenetics of Social Behavior Sector, Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia, koir@bionet.nsc.ru6Laboratory of Neuropathology Modeling, Neurogenetics of Social Behavior Sector, Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia, galyamina@bionet.nsc.ru7Laboratory of Neuropathology Modeling, Neurogenetics of Social Behavior Sector, Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia, n.n.kudryavtseva@gmail.com The activity of ventral tegmental area (VTA) neurons plays a crucial role in the reward circuit, emotional and addictive behaviors in animals and humans. To elucidate the molecular mechanisms underlying the functional changes in VTA neurons under stress arising from social interactions, RNA-Seq analysis was used to compare the transcriptome profiles in the VTA of three groups of male mice: chronically winning mice with positive social experience in daily agonistic interactions, chronically defeated mice with negative social experience in daily agonistic interactions, and control mice having no experience of agonistic interactions. The data obtained showed that both winning and defeated mice experience stress, however, in defeated animals, the repeated agonistic interactions have a stronger effect and cause more significant changes in the levels of gene transcription. Several genes have been identified that may be involved in the determination of alternative behavioral phenotypes in groups of male mice with alternative social experience.

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Genetic mapping of QTLs controlling the ISIAH hypertensive rat behavior in an open field tests

Poster (download) Olga Redina1, Svetlana Smolenskaya2, Arcady Markel31Laboratory. of Evolutional Genetics, Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia, oredina@bionet.nsc.ru2Laboratory of Evolutional Genetics, Wheat Genetics Laboratory, Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia, svsmol@ngs.ru3Laboratory. of Evolutional Genetics, Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia, markel@bionet.nsc.ru Genetic mapping of QTLs controlling the ISIAH hypertensive rat behavior in an open field tests evaluating research behavior, the level of anxiety and motor activity of animals was performed. The work was carried out using two groups of male hybrid rats F2(ISIAHxWAG) of different ages – 3-4 months (n = 103) and 6 months (n = 126) obtained by crossing hypertensive ISIAH and normotensive WAG rats whose behaviors are significantly different in all six tests in an open field taken in the analysis: the latency, the motor activity at 1-st minute of the test, motor activity on the periphery, grooming on the periphery, rearing on the periphery, defecation score. In both groups of rats, genetic loci associated with the studied traits of behavior were found and the common loci associated with both the behavioral traits and traits related to the hypertension development were identified. The results of our work suggest that genes that control behavioral patterns of ISIAH rats can either be closely linked to genes involved in the control of traits associated with the hypertensive status of these rats, or, in some loci, may have a pleiotropic effect on both behavioral traits and on the traits associated with the hypertensive status of ISIAH rats.

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Genome-Centered Integrated Instrumental Information System Modeling and Interpretation of Human and Virus Omics

Anatoliy Shlikht1, Natalia Kramorenko21Far Eastern Federal University, schliht@mail.ru2Far Eastern Federal University, kramnat@mail.ru Creating an integrated genome-centered intellectual system based on highly structured databases and knowledge bases for modeling and interpreting human and virus omics. The system allows you to automatically find functionally significant structures (templates, motifs, epitopes) for genomic and proteomic data in the formation of nucleo-protein complexes and antigen-antibody complexes, determine protein functions, and model spatio-temporal biochemical and physiological processes.

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Results of the whole-genomic sequencing and annotation of the Listeria phenotype

Poster (download) Marina Terekhova11St. Petersburg State University of Information Technologies, Mechanics and Optics, Saint-Petersburg, Russia
, n.mim@mail.ru The incidence of Listeriosis in recent years is constantly increasing. So, in highly developed countries it ranges from 0.3 to 1.5, while in Russia – only 0.04%[1]. Moreover, the indicators in Moscow and St. Petersburg exceed those in the whole country by 4 times, which is explained by the different quality of clinical and laboratory diagnostics. Moreover, mortality due to complications of listeriosis infection can reach 30% [2]. Therefore, the fact of contamination of food products with listeria is of great concern. In this case, the strains of the species L. monocytogenes, L. innocua, L. ivanovii, L. grayii, L. seeligeri, L. welshimeriare most often distinguished. And if earlier it was believed that representatives of the species L. monocytogenespossess the largest set of pathogenicity factors, then the possibilities of molecular and bioinformatics research methods provide a reliable picture with respect to other representatives of the genus Listeria, in particular L. innocua.

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Using fast homology search tools for protein sequence functional annotation: a comparison

Poster (download) Pronozin Artem1, Mikhail Genaev2, Dmitry Afonnikov31lInstitute of Cytology and Genetics SB RAS, pronozinartem95@gmail.com2lInstitute of Cytology and Genetics SB RAS, mag@bionet.nsc.ru3lInstitute of Cytology and Genetics SB RAS, ada@bionet.nsc.ru Annotation of the protein sequences by homology search and GO term transfer from highly homologous sequences is an important task for current genome and transcriptome sequencing projects. However, large size of sequence databases make homologous sequence search difficult in reasonable time. There exist tools that apply fast and ultrafast database search algorithms to find sequence homologs. These tools usually apply various heuristics for fast determining possible sequence matches. This result in different results of these programs with respect to returned set of homologous sequences and their rankings. These differences may lead to differences in the sets of GO terms and lead to errors in query sequence function annotation.В We compare performance of the highly homologous sequence detection by several fast search tools (BLASTP fast, Diamond, Usearch ublast, Usearch local, Mmseq2) applied for A.thaliana protein sequences represented in OrthoDB database. We compared their results with the sequence ranking obtained by ClustalW program for various number k of returned best hits.

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Intermediate and high-risk prostate cancer methylation analysis

Poster (download) Elena Pudova11EIMB RAS, pudova_elena@inbox.ru Prostate cancer is one of the most important socially significant oncological diseases in men. To select an effective approach to therapy, prostate cancer is stratified into appropriate risk groups based on criteria such as TNM status, Gleason score and the level of prostate-specific antigen (PSA). However, to optimize therapy, additional informative markers are necessary, and the aim of this study is to search for these markers at the level of genome methylation. This work included methylation data of prostate cancer from The Cancer Genome Atlas project. The cohort involved patients with high (23 cases) and intermediate (103 cases) risk. As a result, 1,056 differentially methylated CpG sites were found between high and medium risk groups. CpG most interested sites: cg17687367 (chr13: 79936801), cg26874611 (chr5: 168147884), cg06989693 (chr5: 41409252), cg02226810 (chr6: 1605117), cg07736716 (regulation regions: 85): 85 to 91 (85): 85 858: 858: 858: 85: 86: 85: 86: 85: 86: 85: 86: 85: 86: 85: 85.

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RTrans: a pipeline for multi-way analysis of differential gene expression profiles

Poster (download) George Sergeevich Krasnov1, Anastasiya Andreevna Kobelyatskaya2, Anastasiya Vladimirovna Snezhkina3, Vladislav Sergeevich Pavlov4, Elena Anatolevna Pudova5, Anna Victorovna Kudryavtseva61EIMB RAS, gskrasnov@mail.ru2EIMB RAS, kaa.chel@mail.ru3EIMB RAS, leftger@rambler.ru4EIMB RAS, vladislav1pavlov@gmail.com5EIMB RAS, pudova_elena@inbox.ru6EIMB RAS, rhizamoeba@mail.ru RNA-Seq is a widespread technique routinely used to reveal differentially expressed (DE) genes, splicing events and affected signaling pathways. Usually, RNA-Seq data analysis needs skills in programming and bioinformatics. We aimed at developing easy-to-use pipeline covering multiple aspects of DE analysis. Here we present RTrans pipeline aimed at evaluating differential gene expression, pathway enrichment, WGCNA co-expression analysis and visualization. It provides rapid analysis of read counts data including MANOVA, paired tests, non-parametric tests. RTrans represents a versatile pipeline facilitating DE analysis based on RNA-Seq and other quantitative data.

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Differentially expressed genes associated with TMPRSS2-ERG molecular subtype of prostate cancer

Poster (download) Anastasiya Andreevna Kobelyatskaya1, Elena Anatolevna Pudova2, George Sergeevich Krasnov3, Anna Victorovna Kudryavtseva4, Kirill Mikhailovich Nyushko5, Boris Yakovlevich Alekseev61EIMB RAS, kaa.chel@mail.ru2EIMB RAS, pudova_elena@inbox.ru3EIMB RAS, gskrasnov@mail.ru4EIMB RAS, rhizamoeba@mail.ru5FSBI NMRRC, kirandja@yandex.ru6FSBI NMRRC, mnioi@mail.ru Prostate cancer (PC) is one of the most common and socially significant oncological diseases in men. This study examined the transcriptome profile of the most common molecular genetic subtype of prostate cancer, TMPRSS2-ERG. As a result of bioinformatics analysis conducted on the basis of The Cancer Genome Atlas project data, 115 differentially expressed genes were identified for this study group, and in particular, the most over-expressing genes were identified: ALOX15, CACNA1D, EML6, HLA-DMB, NKAIN1, OGDHL, PLA1A, SYT13. Enrichment pathways analysis showed that these genes are participants in important oncologically significant pathways, which emphasizes the association of this molecular subtype with an unfavorable prognosis for prostate cancer.

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Constructing a pipeline for genome variant / gene functioning hybrid prioritization: a case study of type II diabetes

Video (download) Irina Kolesnikova1, Valery Polunovsky2, Konstantin Gunbin31LLC NCGI, Novosibirsk, Russia, i.kolesnikova@mygenetics.ru2LLC NCGI, Novosibirsk, Russia, valeriy.polunovskiy@mygenetics.ru3ICG SB RAS, Novosibirsk, Russia; NSU, Novosibirsk, Russia, genkvg@bionet.nsc.ru According to recently proposed “omnigenic model” the genes implicated in complex diseases determination can be divided into core genes and peripheral genes. Mutations in core genes directly affect disease development, while mutations in peripheral genes can only indirectly modulate disease risk. In this study in order to discriminate core genes and their major regulators, we hierarchically combine genome variant prioritization with the prioritization of genes and target tissues.

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