A5030144117- Gene expression and cancer classification
- Bioinformatics and Genomic Networks
- Cancer Genomics and Diagnostics
- Computational Drug Discovery Methods
- Chromosomal and Genetic Variations
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- Molecular Biology Techniques and Applications
- Colorectal Cancer Treatments and Studies
- Cell Image Analysis Techniques
- Ferroptosis and cancer prognosis
- Cancer, Hypoxia, and Metabolism
- Lung Cancer Treatments and Mutations
- MicroRNA in disease regulation
- Genomics and Phylogenetic Studies
- Glioma Diagnosis and Treatment
- Cancer, Lipids, and Metabolism
- Cancer Research and Treatments
- ATP Synthase and ATPases Research
- Tryptophan and brain disorders
- Advanced Proteomics Techniques and Applications
- Gene Regulatory Network Analysis
- Genomic variations and chromosomal abnormalities
Moscow Institute of Physics and Technology
2021
Architecture Technology Corporation (United States)
2020-2021
Sechenov University
2021
Amway (United States)
2020
Orenburg Regional Clinical Oncology Center
2020
Deutsche Bank (Germany)
2010
Background: Transposons are selfish genetic elements that self-reproduce in host DNA. They were active during evolutionary history and now occupy almost half of mammalian genomes. Close insertions transposons reshaped structure regulation many genes considerably. Co-evolution DNA frequently results the formation new regulatory regions. Previously we published a concept proportion functional features held by positively correlates with rate evolution respective genes. Methods: We ranked human...
High throughput technologies opened a new era in biomedicine by enabling massive analysis of gene expression at both RNA and protein levels. Unfortunately, data obtained different experiments are often poorly compatible, even for the same biologic samples. Here, using experimental bioinformatic investigation major platforms, we show that aggregation level molecular pathways helps to diminish cross- intra-platform bias otherwise clearly seen individual genes. We created mathematical model...
Personalized medicine implies that distinct treatment methods are prescribed to individual patients according several features may be obtained from, e.g., gene expression profile. The majority of machine learning suffer from the deficiency preceding cases, i.e. data on combined with confirmed outcome known methods. At same time, there exist thousands various cell lines were treated hundreds anti-cancer drugs in order check ability these stop proliferation, and all line cultures profiled...
Gastric cancer (GC) is the fifth-ranked type by associated mortality. The proportion of early diagnosis low, and most patients are diagnosed at advanced stages. First-line therapy standardly includes fluoropyrimidines platinum compounds with trastuzumab for HER2-positive cases. For recurrent disease, there several alternative options including ramucirumab, a monoclonal therapeutic antibody that inhibits VEGF-mediated tumor angiogenesis binding VEGFR2, alone or in combination other drugs....
Individual gene expression and molecular pathway activation profiles were shown to be effective biomarkers in many cancers. Here, we used the human interactome model algorithmically build 7470 pathways centered around individual products. We assessed their associations with tumor type survival comparison previous generation of (3022 "classical" pathways) RNA transcripts or proteomic genes, for 8141 1117 samples, respectively. For all analytes data, respectively, found a total 7441 7343...
Endogenous retroviruses and retrotransposons also termed retroelements (REs) are mobile genetic elements that were active until recently in human genome evolution. REs regulate gene expression by actively reshaping chromatin structure or directly providing transcription factor binding sites (TFBS). We aimed to identify molecular processes most deeply impacted the cells at level of TFBS regulation. Using ENCODE data, we identified ~2 million overlapping with putatively regulation-competent...
Harmonization techniques make different gene expression profiles and their sets compatible ready for comparisons. Here we present a new bioinformatic tool termed Shambhala harmonization of multiple human datasets obtained using experimental methods platforms microarray hybridization RNA sequencing.Unlike previously published enabling good quality data only two datasets, allows conversion into the universal form suitable further is based on calibration auxiliary standardization dataset. Each...
Here, we propose a heuristic technique of data trimming for SVM termed FLOating Window Projective Separator (FloWPS), tailored personalized predictions based on molecular data. This procedure can operate with high throughput genetic datasets like gene expression or mutation profiles. Its application prevents from extrapolation by excluding non-informative features. FloWPS requires training the individuals known clinical outcomes to create clinically-relevant classifier. The profiles linked...
(1) Background: Machine learning (ML) methods are rarely used for an omics-based prescription of cancer drugs, due to shortage case histories with clinical outcome supplemented by high-throughput molecular data. This causes overtraining and high vulnerability most ML methods. Recently, we proposed a hybrid global-local approach termed floating window projective separator (FloWPS) that avoids extrapolation in the feature space. Its core property is data trimming, i.e., sample-specific removal...
Abstract Background Machine learning (ML) methods still have limited applicability in personalized oncology due to low numbers of available clinically annotated molecular profiles. This doesn’t allow sufficient training ML classifiers that could be used for improving diagnostics. Methods We reviewed published datasets high throughput gene expression profiles corresponding cancer patients with known responses on chemotherapy treatments. browsed Gene Expression Omnibus (GEO), The Cancer Genome...
Multiple myeloma (MM) affects ~500,000 people and results in ~100,000 deaths annually, being currently considered treatable but incurable. There are several MM chemotherapy treatment regimens, among which eleven include bortezomib, a proteasome-targeted drug. patients respond differently to new prognostic biomarkers needed personalize treatments. However, there is shortage of clinically annotated molecular data that could be used establish novel diagnostics. We report RNA sequencing profiles...
Background: Retroelements (REs) are transposable elements occupying ~40% of the human genome that can regulate genes by providing transcription factor binding sites (TFBS). RE-linked TFBS profile serve as a marker gene transcriptional regulation evolution. This approach allows for interrogating regulatory evolution organisms with RE-rich genomes. We aimed to characterize and molecular pathways using accumulation metric. Methods: characterized either enriched or deficient in regulation. used...
Gliomas are the most common malignant brain tumors with high mortality rates. Recently we showed that FREM2 gene has a role in glioblastoma progression. Here reconstructed molecular pathway using human interactome model. We assessed biomarker capacity of expression and its as overall survival (OS) progression-free (PFS) biomarkers. To this end, used three literature one experimental RNA sequencing datasets collectively covering 566 glioblastomas (GBM) 1097 low-grade gliomas (LGG). The...
Previously, we have shown that the aggregation of RNA-level gene expression profiles into quantitative molecular pathway activation metrics results in lesser batch effects and better agreement between different experimental platforms. Here, investigate whether level data analysis provides any advantage when comparing transcriptomic proteomic data. We compare paired obtained for same human cancer biosamples The Cancer Genome Atlas (TCGA) NCI Clinical Proteomic Tumor Analysis Consortium...
Introduction: Co-normalization of RNA profiles obtained using different experimental platforms and protocols opens avenue for comprehensive comparison relevant features like differentially expressed genes associated with disease. Currently, most bioinformatic tools enable normalization in a flexible format that depends on the individual datasets under analysis. Thus, output data such normalizations will be poorly compatible each other. Recently we proposed new approach to gene expression...
e13143 Background: Anticancer Targeted Drugs (ATDs) specifically target one or a few types of tumor-related molecules in cell. More than two hundred ATDs were approved worldwide. They have different mechanisms action and are effective for cohorts patients. However, many individual cases remain poorly responsive it is great importance to identify predictive markers ATD efficacy. Our aim was develop platform enabling smart selection the most efficient therapies. Methods: We generated...
The evolution of protein-coding genes has both structural and regulatory components. first can be assessed by measuring the ratio non-synonymous to synonymous nucleotide substitutions. second component measured as normalized proportion transposable elements that are used elements. For time, we characterized in parallel evolutionary profiles for 10,890 human 2972 molecular pathways. We observed a ~0.1 correlation between metrics at gene level, which appeared much higher (~0.4) pathway level....
Glioblastoma (GBM) is the most aggressive and lethal central nervous system (CNS) tumor. The treatment strategy mainly surgery and/or radiation therapy, both combined with adjuvant temozolomide (TMZ) chemotherapy. Historically, methylation of
Development of individual predictors clinical drug efficiency becomes the mainstream in modern oncology. According to this approach, for a given patient with known type cancer and chosen drug, we should be able estimate treatment effect caused by drug. Almost all works field apply machine learning techniques, which perform deep statistical analysis set cases supported gene expression data every patient. This important unfortunately, suffers from an essential obstacle: total available is very...
Abstract Background The discovery of RNA interference phenomenon (RNAi) and understanding its mechanisms has revolutionized our views on many molecular processes in the living cell. Among other, RNAi is involved silencing transposable elements inhibition virus infection various eukaryotic organisms. Recent experimental studies demonstrate few cases viral replication suppression via complementary interactions between mammalian small RNAs transcripts. Presentation hypothesis It was found that...
e23142 Background: Anticancer target drugs (ATDs) specifically bind and inhibit molecular targets that play important roles in tumorigenesis. More than 150 different ATDs have been approved for clinical use worldwide, the clinicians are faced with problem of choosing best therapeutic solution each patient. The efficient ATD selection remains largely unsolved personalized approaches needed to select candidates individual patients. Methods: We propose a new approach termed OncoFinder. It is...
Background: Retroelements (REs) are mobile genetic elements comprising ~40% of human DNA. They can reshape expression patterns nearby genes by providing various regulatory sequences. The proportion sequences held REs serve a measure evolution rate the respective and molecular pathways. Methods: We calculated RE-linked enrichment scores for individual pathways based on ENCODE project epigenome data enhancer-specific histone modification H3K4me1 in five cell lines. identified consensus groups...