We overview recent research trends in cancer genomics, bioinformatics tools development and medical genetics, based on results discussed in papers collections “Medical Genetics, Genomics and Bioinformatics” (https://www

A challenge of understanding the mechanisms underlying cognition including neurodevelopmental and neuropsychiatric disorders is mainly given by the potential severity of cognitive disorders for the quality of life and their prevalence. However, the field has been focused predominantly on protein coding variation until recently. Given the importance of tightly controlled gene expression for normal brain function, the goal of the study was to assess the functional variation including non-coding variation in human genome that is likely to play an important role in cognitive functions. To this end, we organized and utilized available genome-wide datasets from genomic, transcriptomic and association studies into a comprehensive data corpus. We focused on genomic regions that are enriched in regulatory activity—overlapping transcriptional factor binding regions and repurpose our data collection especially for identification of the regulatory SNPs (rSNPs) that showed associations both with allele-specific binding and allele-specific expression. We matched these rSNPs to the nearby and distant targeted genes and then selected the variants that could implicate the etiology of cognitive disorders according to Genome-Wide Association Studies (GWAS). Next, we use DeSeq 2.0 package to test the differences in the expression of the certain targeted genes between the controls and the patients that were diagnosed bipolar affective disorder and schizophrenia. Finally, we assess the potential biological role for identified drivers of cognition using DAVID and GeneMANIA. As a result, we selected fourteen regulatory SNPs locating within the loci, implicated from GWAS for cognitive disorders with six of the variants unreported previously. Grouping of the targeted genes according to biological functions revealed the involvement of processes such as ‘posttranscriptional regulation of gene expression’, ‘neuron differentiation’, ‘neuron projection development’, ‘regulation of cell cycle process’ and ‘protein catabolic processes’. We identified four rSNP-targeted genes that showed differential expression between patient and control groups depending on brain region: NRAS—in schizophrenia cohort, CDC25B, DDX21 and NUCKS1—in bipolar disorder cohort. Overall, our findings are likely to provide the keys for unraveling the mechanisms that underlie cognitive functions including major depressive disorder, bipolar disorder and schizophrenia etiopathogenesis.

Aim: According to the current data, a major factor for phenotypic variation of complex traits and disease susceptibility is the cis-acting effects of noncoding variants on gene expression. Our purpose was to evaluate the association between colorectal cancer (CRC) and six single nucleotide polymorphisms identified using our original bioinformatics approach as regulatory and putatively related to CRC. Materials: One hundred and sixty CRC patients and 185 healthy controls have been genotyped for rs590352, rs2072580, rs78317230, rs3829202, rs11542583 and rs4796672. Results: Genotypes and alleles distributions of rs590352 of ATXN7L3B gene were significantly different between the male CRC subjects and controls. Significant correlation of genotype with CRC is observable for women only for the rs4796672 of KRT15 gene. Analysis of haplotypes reveals that rs2072580 of the ISCU and SART3 genes can be also associated with CRC. Conclusion: We have identified three SNPs associated with CRC risk and demonstrated a gender specificity of rs590352 and rs4796672.

Разработан новый подход к поиску регуляторных SNP (rSNP), основанный на анализе ChIP-seq и RNA-seq данных проекта ENCODE. Подход успешно применен для выявления rSNP, связанных с колоректальным раком. В качестве исходных данных были взяты результаты 15 независимых ChIP-Seq экспериментов, выполненных на клеточной линии колоректального рака HCT-116, что позволило сформировать пул из 7985 SNP, расположенных в регуляторных районах генов. Для дальнейшего отбора регуляторных SNP из этого пула использована выявляемая в экспериментах ChIP-seq аллель-специфичность распределения гистоновых меток и негистоновых белков хроматина в местах локализации гетерозиготных SNP. Это позволило выявить 775 SNP, которые потенциально могут влиять на уровень экспрессии генов в клетках HCT-116. В дальнейшем была проведена оценка асимметричности экспрессии аллелей на основании данных RNA-seq, полученных на той же клеточной линии. В результате была подтверждена функциональность 231 SNP, которые были классифицированы как rSNP. Для отбора из них тех, что могут иметь отношение к развитию колоректального рака, были взяты rSNP, находящиеся в одной группе сцепления (±10 т. п. н.) с SNP, ассоциированными с этим заболеванием, по данным GWAS и ClinVar. Функциональная аннотация генов, содержащих выбранные таким образом SNP, подтвердила полученные ранее данные о роли генов BAIAP2L1 и BUB3 в формировании предрасположенности к раку толстого кишечника. Также были обнаружены новые гены-кандидаты колоректального рака, RRAGD и FZD6, белковые продукты которых являются компонентами RAS/MAРK- и WNT-сигнальных путей, сопряженных с развитием данной патологии. Кроме того, выявлено 14 новых потенциальных генов-кандидатов колоректального рака, перспективных для дальнейшего изучения.