Search results for " code"

Basic Concepts in Molecular Biology Related to Genetics and Epigenetics.

2017

The observation that "one size does not fit all" for the prevention and treatment of cardiovascular disease, among other diseases, has driven the concept of precision medicine. The goal of precision medicine is to provide the best-targeted interventions tailored to an individual's genome. The human genome is composed of billions of sequence arrangements containing a code that controls how genes are expressed. This code depends on other nonstatic regulators that surround the DNA and constitute the epigenome. Moreover, environmental factors also play an important role in this complex regulation. This review provides a general perspective on the basic concepts of molecular biology related to g…

Comprehensive evaluation of coding region point mutations in microsatellite-unstable colorectal cancer

2018

Microsatellite instability (MSI) leads to accumulation of an excessive number of mutations in the genome, mostly small insertions and deletions. MSI colorectal cancers (CRCs), however, also contain more point mutations than microsatellite-stable (MSS) tumors, yet they have not been as comprehensively studied. To identify candidate driver genes affected by point mutations in MSI CRC, we ranked genes based on mutation significance while correcting for replication timing and gene expression utilizing an algorithm, MutSigCV. Somatic point mutation data from the exome kit-targeted area from 24 exome-sequenced sporadic MSI CRCs and respective normals, and 12 whole-genome-sequenced sporadic MSI CR…

Transcriptomic and Genetic Associations between Alzheimer's Disease, Parkinson's Disease, and Cancer.

2021

Simple Summary Epidemiological studies have identified a link between neurodegenerative disorders and a reduced risk of overall cancer. Increases and decreases in the risk of site-specific cancers have also been reported. However, it is still unknown whether these associations arise due to shared genetic and molecular factors or are explained by other phenomena (e.g., biases in epidemiological studies or the use of medication). In this study, we aimed to investigate the potential molecular, genetic, and pharmacological links between Alzheimer’s and Parkinson’s diseases and a large panel of 22 cancer types. To examine the overlapping involvement of genes and pathways, we obtained differentia…

Epigenomic landscape of human colorectal cancer unveils an aberrant core of pan-cancer enhancers orchestrated by YAP/TAZ

2021

Cancer is characterized by pervasive epigenetic alterations with enhancer dysfunction orchestrating the aberrant cancer transcriptional programs and transcriptional dependencies. Here, we epigenetically characterize human colorectal cancer (CRC) using de novo chromatin state discovery on a library of different patient-derived organoids. By exploring this resource, we unveil a tumor-specific deregulated enhancerome that is cancer cell-intrinsic and independent of interpatient heterogeneity. We show that the transcriptional coactivators YAP/TAZ act as key regulators of the conserved CRC gained enhancers. The same YAP/TAZ-bound enhancers display active chromatin profiles across diverse human t…

2016

The growth of next-generation sequencing (NGS) datasets poses a challenge to the alignment of reads to reference genomes in terms of alignment quality and execution speed. Some available aligners have been shown to obtain high quality mappings at the expense of long execution times. Finding fast yet accurate software solutions is of high importance to research, since availability and size of NGS datasets continue to increase. In this work we present an efficient parallelization approach for NGS short-read alignment on multi-core clusters. Our approach takes advantage of a distributed shared memory programming model based on the new UPC++ language. Experimental results using the CUSHAW3 alig…

3-Dimensional Analysis and Systematic Review of Root Canal Morphology and Physiological Foramen Geometry of 109 Mandibular First Premolars by Micro-c…

2019

Abstract Introduction The aim of this study was to systematically revise the root canal configuration (RCC) literature and to investigate the root canal morphology of mandibular first premolars (Ma1Ps) of 2 populations by means of micro–computed tomographic imaging. Methods This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines including RCC randomized controlled trials and cross-sectional, cohort, comparative, validation, and evaluation studies. Furthermore, the RCC, physiological foramina, the frequency of accessory and connecting canals, and the physiological foramina morphology of 109 Ma1Ps were investigated by means of micro–co…

Root Canal Morphology of 116 Maxillary Second Premolars by Micro–Computed Tomography in a Mixed Swiss-German Population with Systematic Review

2020

Abstract Introduction The aim of this investigation was to examine the root canal system morphology of maxillary second premolars (Mx2Ps) of a Swiss-German population by means of micro–computed tomography and provide systematic review of the root canal configuration (RCC) literature of Mx2Ps. Methods The RCC, main foramina as well as accessory canals and foramina frequency of 116 Mx2Ps, were investigated by means of micro–computed tomography and 3-dimensional software imaging. The RCC from the coronal to apical thirds of the root as well as the main foramina number were described by using a four-digit system code. The literature review follows the PRISMA guideline analyzing randomized contr…

Role of glutathione in the regulation of epigenetic mechanisms in disease

2017

Epigenetics is a rapidly growing field that studies gene expression modifications not involving changes in the DNA sequence. Histone H3, one of the basic proteins in the nucleosomes that make up chromatin, is S-glutathionylated in mammalian cells and tissues, making Gamma-L-glutamyl-L-cysteinylglycine, glutathione (GSH), a physiological antioxidant and second messenger in cells, a new post-translational modifier of the histone code that alters the structure of the nucleosome. However, the role of GSH in the epigenetic mechanisms likely goes beyond a mere structural function. Evidence supports the hypothesis that there is a link between GSH metabolism and the control of epigenetic mechanisms…

parSRA: A framework for the parallel execution of short read aligners on compute clusters

2018

The growth of next generation sequencing datasets poses as a challenge to the alignment of reads to reference genomes in terms of both accuracy and speed. In this work we present parSRA, a parallel framework to accelerate the execution of existing short read aligners on distributed-memory systems. parSRA can be used to parallelize a variety of short read alignment tools installed in the system without any modification to their source code. We show that our framework provides good scalability on a compute cluster for accelerating the popular BWA-MEM and Bowtie2 aligners. On average, it is able to accelerate sequence alignments on 16 64-core nodes (in total, 1024 cores) with speedup of 10.48 …

Evidence for the implication of the histone code in building the genome structure

2018

International audience; Histones are punctuated with small chemical modifications that alter their interaction with DNA. One attractive hypothesis stipulates that certain combinations of these histone modifications may function, alone or together, as a part of a predictive histone code to provide ground rules for chromatin folding. We consider four features that relate histone modifications to chromatin folding: charge neutralisation, molecular specificity, robustness and evolvability. Next, we present evidence for the association among different histone modifications at various levels of chromatin organisation and show how these relationships relate to function such as transcription, repli…