A method of gene expression data transfer from cell lines to cancer patients for machine-learning prediction of drug efficiency.

Personalized medicine implies that distinct treatment methods are prescribed to individual patients according several features that may be obtained from, e.g., gene expression profile.

Gene expression and molecular pathway activation signatures of -amplified neuroblastomas.

Neuroblastoma is a pediatric cancer arising from sympathetic nervous system. Remarkable heterogeneity in outcomes is one of its widely known features. One of the traits strongly associated with the unfavorable subtype is the amplification of oncogene .

Potentialities of MicroRNA Diagnosis in Patients with Bladder Cancer.

Despite promising vista of the use of microRNA in molecular diagnosis of bladder cancer, there are few data on their expression profiles, which impedes assessment of diagnostic value of these marker molecules. In this study, suppression subtractive hybridization, on-chip hybridization, and high-throughput deep sequencing focused on profiling microRNA and assessing the diagnostic value of revealed marker molecules.

Bioinformatics Meets Biomedicine: OncoFinder, a Quantitative Approach for Interrogating Molecular Pathways Using Gene Expression Data.

We propose a biomathematical approach termed OncoFinder (OF) that enables performing both quantitative and qualitative analyses of the intracellular molecular pathway activation. OF utilizes an algorithm that distinguishes the activator/repressor role of every gene product in a pathway. This method is applicable for the analysis of any physiological, stress, malignancy, and other conditions at the molecular level.

Mathematical Justification of Expression-Based Pathway Activation Scoring (PAS).

Although modeling of activation kinetics for various cell signaling pathways has reached a high grade of sophistication and thoroughness, most such kinetic models still remain of rather limited practical value for biomedicine. Nevertheless, recent advancements have been made in application of signaling pathway science for real needs of prescription of the most effective drugs for individual patients. The methods for such prescription evaluate the degree of pathological changes in the signaling machinery based on two types of data: first, on the results of high-throughput gene expression profiling, and second, on the molecular pathway graphs that reflect interactions between the pathway members.

Data aggregation at the level of molecular pathways improves stability of experimental transcriptomic and proteomic data.

High throughput technologies opened a new era in biomedicine by enabling massive analysis of gene expression at both RNA and protein levels. Unfortunately, expression data obtained in different experiments are often poorly compatible, even for the same biologic samples. Here, using experimental and bioinformatic investigation of major experimental platforms, we show that aggregation of gene expression data at the level of molecular pathways helps to diminish cross- and intra-platform bias otherwise clearly seen at the level of individual genes.

Temporary portal vein embolization is as efficient as permanent portal vein embolization in mice.

Background: Temporary portal vein embolization may be a safe alternative to permanent portal vein embolization. Such a new approach could be applied in living-related liver transplantation to increase graft volume before procurement. The impact of temporary portal vein embolization on occluded liver after recanalization, however, has never been assessed.

Early stage of cytomegalovirus infection suppresses host microRNA expression regulation in human fibroblasts.

Responses to human cytomegalovirus (HCMV) infection are largely individual and cell type specific. We investigated molecular profiles in 2 primary cell cultures of human fibroblasts, which are highly or marginally sensitive to HCMV infection, respectively. We screened expression of genes and microRNAs (miRs) at the early (3 hours) stage of infection.

Molecular pathway activation features of pediatric acute myeloid leukemia (AML) and acute lymphoblast leukemia (ALL) cells.

Acute lymphoblast leukemia (ALL) is characterized by overproduction of immature white blood cells in the bone marrow. ALL is most common in the childhood and has high (>80%) cure rate. In contrast, acute myeloid leukemia (AML) has far greater mortality rate than the ALL and is most commonly affecting older adults.

MiRImpact, a new bioinformatic method using complete microRNA expression profiles to assess their overall influence on the activity of intracellular molecular pathways.

MicroRNAs (miRs) are short noncoding RNA molecules that regulate expression of target mRNAs. Many published sources provide information about miRs and their targets. However, bioinformatic tools elucidating higher level impact of the established total miR profiles, are still largely missing.

[Receptor tyrosine kinase KIT may regulate expression of genes involved in spontaneous regression of neuroblastoma].

Hallmark of neuroblastoma is an ability of this malignant tumor to undergo spontaneous regression or differentiation into benign tumor during any stage of the disease, but it is little known about mechanisms of these phenomena. We studied effect of receptor tyrosine kinase receptor KIT on expression of genes, which may be involved in tumor spontaneous regression. Downregulation of KIT expression by RNA interference in SH-SY5Y cells causes suppression of neurotrophin receptor NGFR expression that may promote the loss of sensibility of cells to nerve growth factors, also it causes upregulation of TrkA receptor expression which can stimulate cell differentiation or apoptosis in NGF dependent manner.

Molecular pathway activation features linked with transition from normal skin to primary and metastatic melanomas in human.

Melanoma is the most aggressive and dangerous type of skin cancer, but its molecular mechanisms remain largely unclear. For transcriptomic data of 478 primary and metastatic melanoma, nevi and normal skin samples, we performed high-throughput analysis of intracellular molecular networks including 592 signaling and metabolic pathways. We showed that at the molecular pathway level, the formation of nevi largely resembles transition from normal skin to primary melanoma.

A method for predicting target drug efficiency in cancer based on the analysis of signaling pathway activation.

A new generation of anticancer therapeutics called target drugs has quickly developed in the 21st century. These drugs are tailored to inhibit cancer cell growth, proliferation, and viability by specific interactions with one or a few target proteins. However, despite formally known molecular targets for every "target" drug, patient response to treatment remains largely individual and unpredictable.

Combinatorial high-throughput experimental and bioinformatic approach identifies molecular pathways linked with the sensitivity to anticancer target drugs.

Effective choice of anticancer drugs is important problem of modern medicine. We developed a method termed OncoFinder for the analysis of new type of biomarkers reflecting activation of intracellular signaling and metabolic molecular pathways. These biomarkers may be linked with the sensitivity to anticancer drugs.

Signaling pathway cloud regulation for in silico screening and ranking of the potential geroprotective drugs.

The major challenges of aging research include absence of the comprehensive set of aging biomarkers, the time it takes to evaluate the effects of various interventions on longevity in humans and the difficulty extrapolating the results from model organisms to humans. To address these challenges we propose the in silico method for screening and ranking the possible geroprotectors followed by the high-throughput in vivo and in vitro validation. The proposed method evaluates the changes in the collection of activated or suppressed signaling pathways involved in aging and longevity, termed signaling pathway cloud, constructed using the gene expression data and epigenetic profiles of young and old patients' tissues.

Genetics and epigenetics of aging and longevity.

Evolutionary theories of aging predict the existence of certain genes that provide selective advantage early in life with adverse effect on lifespan later in life (antagonistic pleiotropy theory) or longevity insurance genes (disposable soma theory). Indeed, the study of human and animal genetics is gradually identifying new genes that increase lifespan when overexpressed or mutated: gerontogenes. Furthermore, genetic and epigenetic mechanisms are being identified that have a positive effect on longevity.

A systematic experimental evaluation of microRNA markers of human bladder cancer.

Background: MicroRNAs (miRNAs) are a class of small RNAs that regulate gene expression. They are aberrantly expressed in many human cancers and are potential therapeutic targets and molecular biomarkers.

Methods: In this study, we for the first time validated the reported data on the entire set of published differential miRNAs (102 in total) through a series of transcriptome-wide experiments.