Search results for "COMPUTATION"
showing 10 items of 7362 documents
The Anemonia viridis Venom: Coupling Biochemical Purification and RNA-Seq for Translational Research
2018
Blue biotechnologies implement marine bio-resources for addressing practical concerns. The isolation of biologically active molecules from marine animals is one of the main ways this field develops. Strikingly, cnidaria are considered as sustainable resources for this purpose, as they possess unique cells for attack and protection, producing an articulated cocktail of bioactive substances. The Mediterranean sea anemone Anemonia viridis has been studied extensively for years. In this short review, we summarize advances in bioprospecting of the A. viridis toxin arsenal. A. viridis RNA datasets and toxin data mining approaches are briefly described. Analysis reveals the major pool of neurotoxi…
Subtracting the sequence bias from partially digested MNase-seq data reveals a general contribution of TFIIS to nucleosome positioning.
2017
Background TFIIS stimulates RNA cleavage by RNA polymerase II and promotes the resolution of backtracking events. TFIIS acts in the chromatin context, but its contribution to the chromatin landscape has not yet been investigated. Co-transcriptional chromatin alterations include subtle changes in nucleosome positioning, like those expected to be elicited by TFIIS, which are elusive to detect. The most popular method to map nucleosomes involves intensive chromatin digestion by micrococcal nuclease (MNase). Maps based on these exhaustively digested samples miss any MNase-sensitive nucleosomes caused by transcription. In contrast, partial digestion approaches preserve such nucleosomes, but intr…
A gene expression inflammatory signature specifically predicts multiple myeloma evolution and patients survival
2016
AbstractMultiple myeloma (MM) is closely dependent on cross-talk between malignant plasma cells and cellular components of the inflammatory/immunosuppressive bone marrow milieu, which promotes disease progression, drug resistance, neo-angiogenesis, bone destruction and immune-impairment. We investigated the relevance of inflammatory genes in predicting disease evolution and patient survival. A bioinformatics study by Ingenuity Pathway Analysis on gene expression profiling dataset of monoclonal gammopathy of undetermined significance, smoldering and symptomatic-MM, identified inflammatory and cytokine/chemokine pathways as the most progressively affected during disease evolution. We then sel…
Intermittent targeted therapies and stochastic evolution in patients affected by chronic myeloid leukemia
2016
Front line therapy for the treatment of patients affected by chronic myeloid leukemia (CML) is based on the administration of tyrosine kinase inhibitors, namely imatinib or, more recently, axitinib. Although imatinib is highly effective and represents an example of a successful molecular targeted therapy, the appearance of resistance is observed in a proportion of patients, especially those in advanced stages. In this work, we investigate the appearance of resistance in patients affected by CML, by modeling the evolutionary dynamics of cancerous cell populations in a simulated patient treated by an intermittent targeted therapy. We simulate, with the Monte Carlo method, the stochastic evolu…
Dissection of DLBCL microenvironment provides a gene expression-based predictor of survival applicable to formalin-fixed paraffin-embedded tissue
2018
Abstract Background Gene expression profiling (GEP) studies recognized a prognostic role for tumor microenvironment (TME) in diffuse large B-cell lymphoma (DLBCL), but the routinely adoption of prognostic stromal signatures remains limited. Patients and methods Here, we applied the computational method CIBERSORT to generate a 1028-gene matrix incorporating signatures of 17 immune and stromal cytotypes. Then, we carried out a deconvolution on publicly available GEP data of 482 untreated DLBCLs to reveal associations between clinical outcomes and proportions of putative tumor-infiltrating cell types. Forty-five genes related to peculiar prognostic cytotypes were selected and their expression …
A practical method for barcoding and size-trimming PCR templates for amplicon sequencing
2016
Sample barcoding facilitates the analysis of tens or even hundreds of samples in a single next-generation sequencing (NGS) run, but more efficient methods are needed for high-throughput barcoding and size-trimming of long PCR products. Here we present a two-step PCR approach for barcoding followed by pool shearing, adapter ligation, and 5′ end selection for trimming sets of DNA templates of any size. Our new trimming method offers clear benefits for phylogenetic studies, since targeting exactly the same region maximizes the alignment and enables the use of operational taxonomic unit (OTU)-based algorithms.
Optimization of Lead Placement in the Right Ventricle During Cardiac Resynchronization Therapy. A Simulation Study
2019
[EN] Patients suffering from heart failure and left bundle branch block show electrical ventricular dyssynchrony causing an abnormal blood pumping. Cardiac resynchronization therapy (CRT) is recommended for these patients. Patients with positive therapy response normally present QRS shortening and an increased left ventricle (LV) ejection fraction. However, around one third do not respond favorably. Therefore, optimal location of pacing leads, timing delays between leads and/or choosing related biomarkers is crucial to achieve the best possible degree of ventricular synchrony during CRT application. In this study, computational modeling is used to predict the optimal location and delay of p…
Developmental transcriptomics in Atlantic haddock: Illuminating pattern formation and organogenesis in non-model vertebrates.
2016
Gadiforms such as Atlantic haddock comprise some of the world's most economically important fisheries. Understanding the early life history of these fish is a prerequisite for predicting effects of a changing environment and increased human activities. Robust assessment of the effects of environmental impacts on the embryos of non-model vertebrates is hampered by a lack of molecular resources and detailed knowledge regarding the regulation of genes and pathways in early development. Here we used mRNA sequencing to link transcriptional changes to developmental processes in haddock, specifically, pattern formation and organogenesis. Temporal expression of key developmental genes was tightly a…
Small endogenous molecules as moiety to improve targeting of CNS drugs.
2016
A major challenge in the development of novel neuro-therapeutic agents is to effectively overcome the blood-brain barrier (BBB), which acts as a 'working dynamic barrier'. The core problem in the treatment of neurodegenerative diseases is failed delivery of potential medicines due to their inadequate permeation rate. Areas covered: The present review gives a summary of endogenous moieties used in synthesizing prodrugs, derivatives and bioisosteric drugs appositely designed to structurally resemble physiological molecular entities able to be passively absorbed or carried by specific carrier proteins expressed at BBB level. In particular, this overview focuses on aminoacidic, glycosyl, purine…
Cardenolides: Insights from chemical structure and pharmacological utility
2019
Cardiac glycosides (CGs) are a class of naturally occurring steroid-like compounds, and members of this class have been in clinical use for more than 1500 years. They have been used in folk medicine as arrow poisons, abortifacients, heart tonics, emetics, and diuretics as well as in other applications. The major use of CGs today is based on their ability to inhibit the membrane-bound Na