Genomic diversity of populations from different regions of the human stomach.

Individuals infected with harbor unique and diverse populations of quasispecies, but diversity between and within different regions of the human stomach and the process of bacterial adaptation to each location are not yet well understood. We applied whole-genome deep sequencing to characterize the within- and between-stomach region genetic diversity populations from paired antrum and corpus biopsies of 15 patients, along with single biopsies from one region of an additional 3 patients, by scanning allelic diversity. We combined population deep sequencing with more conventional sequencing of multiple single colony isolates from individual biopsies to generate a unique dataset.

Immune dysfunction signatures predict outcomes and define checkpoint blockade-unresponsive microenvironments in acute myeloid leukemia.

BackgroundImmune exhaustion and senescence are dominant dysfunctional states of effector T cells and major hurdles for the success of cancer immunotherapy. In the current study, we characterized how acute myeloid leukemia (AML) promotes the generation of senescent-like CD8+ T cells and whether they have prognostic relevance.METHODSWe analyzed NanoString, bulk RNA-Seq and single-cell RNA-Seq data from independent clinical cohorts comprising 1,896 patients treated with chemotherapy and/or immune checkpoint blockade (ICB).

Hyperactive neutrophil chemotaxis contributes to anti-tumor necrosis factor-α treatment resistance in inflammatory bowel disease.

Background And Aim: Anti-tumor necrosis factor-α (anti-TNF-α) agents have been used for inflammatory bowel disease; however, it has up to 30% nonresponse rate. Identifying molecular pathways and finding reliable diagnostic biomarkers for patient response to anti-TNF-α treatment are needed.

Methods: Publicly available transcriptomic data from inflammatory bowel disease patients receiving anti-TNF-α therapy were systemically collected and integrated.

Faecal microRNAs as a non-invasive tool in the diagnosis of colonic adenomas and colorectal cancer: A meta-analysis.

MicroRNAs (miRNAs) are proposed as potential biomarkers for the diagnosis of numerous diseases. Here, we performed a meta-analysis to evaluate the utility of faecal miRNAs as a non-invasive tool in colorectal cancer (CRC) screening. A systematic literature search, according to predetermined criteria, in five databases identified 17 research articles including 6475, 783 and 5569 faecal-based miRNA tests in CRC, adenoma patients and healthy individuals, respectively.

Phylogeographic separation and formation of sexually discrete lineages in a global population of .

is a Gram-negative intestinal pathogen of humans and has been responsible for several nationwide gastrointestinal outbreaks. Large-scale population genomic studies have been performed on the other human pathogenic species of the genus and allowing a high-resolution understanding of the ecology, evolution and dissemination of these pathogens. However, to date no purpose-designed large-scale global population genomic analysis of has been performed.

Elevated mitochondrial genome variation after 50 generations of radiation exposure in a wild rodent.

Currently, the effects of chronic, continuous low dose environmental irradiation on the mitochondrial genome of resident small mammals are unknown. Using the bank vole () as a model system, we tested the hypothesis that approximately 50 generations of exposure to the Chernobyl environment has significantly altered genetic diversity of the mitochondrial genome. Using deep sequencing, we compared mitochondrial genomes from 131 individuals from reference sites with radioactive contamination comparable to that present in northern Ukraine before the 26 April 1986 meltdown, to populations where substantial fallout was deposited following the nuclear accident.

AGAPE (Automated Genome Analysis PipelinE) for pan-genome analysis of Saccharomyces cerevisiae.

The characterization and public release of genome sequences from thousands of organisms is expanding the scope for genetic variation studies. However, understanding the phenotypic consequences of genetic variation remains a challenge in eukaryotes due to the complexity of the genotype-phenotype map. One approach to this is the intensive study of model systems for which diverse sources of information can be accumulated and integrated.

Cronobacter, the emergent bacterial pathogen Enterobacter sakazakii comes of age; MLST and whole genome sequence analysis.

Background: Following the association of Cronobacter spp. to several publicized fatal outbreaks in neonatal intensive care units of meningitis and necrotising enterocolitis, the World Health Organization (WHO) in 2004 requested the establishment of a molecular typing scheme to enable the international control of the organism. This paper presents the application of Next Generation Sequencing (NGS) to Cronobacter which has led to the establishment of the Cronobacter PubMLST genome and sequence definition database (http://pubmlst.

Maternal age effect and severe germ-line bottleneck in the inheritance of human mitochondrial DNA.

The manifestation of mitochondrial DNA (mtDNA) diseases depends on the frequency of heteroplasmy (the presence of several alleles in an individual), yet its transmission across generations cannot be readily predicted owing to a lack of data on the size of the mtDNA bottleneck during oogenesis. For deleterious heteroplasmies, a severe bottleneck may abruptly transform a benign (low) frequency in a mother into a disease-causing (high) frequency in her child. Here we present a high-resolution study of heteroplasmy transmission conducted on blood and buccal mtDNA of 39 healthy mother-child pairs of European ancestry (a total of 156 samples, each sequenced at ∼20,000× per site).

Controlling for contamination in re-sequencing studies with a reproducible web-based phylogenetic approach.

Polymorphism discovery is a routine application of next-generation sequencing technology where multiple samples are sent to a service provider for library preparation, subsequent sequencing, and bioinformatic analyses. The decreasing cost and advances in multiplexing approaches have made it possible to analyze hundreds of samples at a reasonable cost. However, because of the manual steps involved in the initial processing of samples and handling of sequencing equipment, cross-contamination remains a significant challenge.

Is genomics bad for you?

The plasticity of the genome complicates genetic causation but should be investigated from a functional perspective. Specific adaptive hypotheses are referenced in the target article, but it is also necessary to explain how the integrity of the genome is maintained despite processes that tend towards its diversification and degradation. These include the accumulation of deleterious changes and intragenomic conflict.

Revealing mammalian evolutionary relationships by comparative analysis of gene clusters.

Many software tools for comparative analysis of genomic sequence data have been released in recent decades. Despite this, it remains challenging to determine evolutionary relationships in gene clusters due to their complex histories involving duplications, deletions, inversions, and conversions. One concept describing these relationships is orthology.

Dynamics of mitochondrial heteroplasmy in three families investigated via a repeatable re-sequencing study.

Background: Originally believed to be a rare phenomenon, heteroplasmy - the presence of more than one mitochondrial DNA (mtDNA) variant within a cell, tissue, or individual - is emerging as an important component of eukaryotic genetic diversity. Heteroplasmies can be used as genetic markers in applications ranging from forensics to cancer diagnostics. Yet the frequency of heteroplasmic alleles may vary from generation to generation due to the bottleneck occurring during oogenesis.

High-resolution mapping of evolutionary trajectories in a phage.

Experimental evolution in rapidly reproducing viruses offers a robust means to infer substitution trajectories during evolution. But with conventional approaches, this inference is limited by how many individual genotypes can be sampled from the population at a time. Low-frequency changes are difficult to detect, potentially rendering early stages of adaptation unobservable.

Wheels within wheels: clues to the evolution of the Gnas and Gnal loci.

The Gnas and Gnal loci, which encode the alpha subunits of stimulatory G-proteins, are among the most complex eukaryotic genes. They combine elaborate patterns of imprinting, alternative splicing, and antisense transcription with tissue- and developmental stage-specific expression. Different regions of these genes evolve at drastically different rates such that some show complete conservation, whereas others are virtually unalignable.

Imprinted genes, postnatal adaptations and enduring effects on energy homeostasis.

The effects of imprinted genes on fetal growth and development have been firmly established. By and large, their roles conform to a conflict over provision of limited maternal resources to offspring, such that paternally expressed imprinted genes in offspring generally promote growth of the fetus, while maternally expressed imprinted genes tend to restrict it. It is comparatively recently that the important effects of imprinted genes in postnatal physiology have begun to be demonstrated, although a similar conflict may apply.