scholarly journals The genomic context for aflatoxin B1-degrading Pseudomonas strains

2021 ◽  
Author(s):  
Jiahong Tang ◽  
Dun Deng ◽  
Maopeng Song ◽  
Zhichang Liu ◽  
Sanmei Ma ◽  
...  
Keyword(s):  
Genomic Context ◽  
Oxidoreductase Activity ◽  
Protein Coding ◽  
Genome Wide ◽  
Whole Genomes ◽  
Pseudomonas Species ◽  
Protein Functions ◽  
Clusters Of Orthologous Groups ◽  
Enzyme Families ◽  
Reference Genomes

AbstractThe whole genomes of three strains were sequenced and annotated. COG (Clusters of Orthologous Groups) and GO (Gene Ontology) annotations of the protein-coding genes from three strains show a conservation of genome-wide protein functions in genus Pseudomonas. However, the AFB1-degrading strains HAI2 and HT3 harbor much more genes belonged to the pathway of xenobiotics biodegradation and metabolism than non-degrading strain 48. Besides, the enzyme families potentially involved in the AFB1 degradation of bacteria are more abundant in the two AFB1-degrading strains. A pan-genome profile was then formed by comparing the genomes against other reference genomes of the corresponding Pseudomonas species. Accordingly, a total of 1,528 genes were found to be specific in AFB1-degrading strains, and 65 genes of them are related to oxidoreductase activity.

scholarly journals Deep Annotation of Protein Function across Diverse Bacteria from Mutant Phenotypes

2016 ◽  
Author(s):  
Morgan N. Price ◽  
Kelly M. Wetmore ◽  
R. Jordan Waters ◽  
Mark Callaghan ◽  
Jayashree Ray ◽  
...  
Keyword(s):  
Protein Function ◽  
Large Scale ◽  
Hypothetical Proteins ◽  
Data Set ◽  
Protein Coding ◽  
Bacterial Proteins ◽  
Genome Wide ◽  
Protein Functions ◽  
Mutant Phenotypes ◽  
Related Proteins

SummaryThe function of nearly half of all protein-coding genes identified in bacterial genomes remains unknown. To systematically explore the functions of these proteins, we generated saturated transposon mutant libraries from 25 diverse bacteria and we assayed mutant phenotypes across hundreds of distinct conditions. From 3,903 genome-wide mutant fitness assays, we obtained 14.9 million gene phenotype measurements and we identified a mutant phenotype for 8,487 proteins with previously unknown functions. The majority of these hypothetical proteins (57%) had phenotypes that were either specific to a few conditions or were similar to that of another gene, thus enabling us to make informed predictions of protein function. For 1,914 of these hypothetical proteins, the functional associations are conserved across related proteins from different bacteria, which confirms that these associations are genuine. This comprehensive catalogue of experimentally-annotated protein functions also enables the targeted exploration of specific biological processes. For example, sensitivity to a DNA-damaging agent revealed 28 known families of DNA repair proteins and 11 putative novel families. Across all sequenced bacteria, 14% of proteins that lack detailed annotations have an ortholog with a functional association in our data set. Our study demonstrates the utility and scalability of high-throughput genetics for large-scale annotation of bacterial proteins and provides a vast compendium of experimentally-determined protein functions across diverse bacteria.

scholarly journals Genome-wide identification and functional analysis of circRNAs in Zea mays

2018 ◽  
Author(s):  
Baihua Tang ◽  
Zhiqiang Hao ◽  
Yanfeng Zhu ◽  
Hua Zhang ◽  
Guanglin Li
Keyword(s):  
Gene Expression ◽  
Zea Mays ◽  
High Throughput Sequencing ◽  
Circular Rnas ◽  
Biological Functions ◽  
Molecular Processes ◽  
Oxidoreductase Activity ◽  
Protein Coding ◽  
Genome Wide ◽  
And Function

AbstractCircular RNAs (circRNAs) are a class of endogenous noncoding RNAs, which increasingly drawn researchers’ attention in recent years as their importance in regulating gene expression at the transcriptional and post-transcriptional levels. With the development of high-throughput sequencing and bioinformatics, circRNAs have been widely analysed in animals, but the understanding of characteristics and function of circRNAs is limited in plants, especially in maize. Here, 3715 unique circRNAs were predicted in Zea mays systematically, and 8 of 12 circRNAs were validated by experiments. By analysing circRNA sequence, the events of alternative circularization phenomenon were found prevailed in maize. By comparing circRNAs in different species, it showed that part circRNAs are conserved across species, for example, there are 273 circRNAs conserved between maize and rice. Although most of the circRNAs have low expression levels, we found 213 differential expressed circRNAs responding to heat, cold, or drought, and 1782 tissue-specific expressed circRNAs. The results showed that those circRNAs may have potential biological functions in specific situations. Finally, two different methods were used to search circRNA functions, which were based on circRNAs originated from protein-coding genes and circRNAs as miRNA decoys. 346 circRNAs could act as miRNA decoys, which might modulate the effects of multiple molecular functions, including binding, catalytic activity, oxidoreductase activity, and transmembrane transporter activity. Maize circRNAs were identified, classified and characterized systematically. We also explored circRNA functions, suggesting that circRNAs are involved in multiple molecular processes and play important roles in regulating of gene expression. Our results provide a rich resource for further study of maize circRNAs.

scholarly journals Genome-Wide Reconstitution of Chromatin Transactions: RSC Preferentially disrupts H2A.Z-Containing Nucleosomes

2018 ◽  
Author(s):  
Aylin Cakiroglu ◽  
Cedric R. Clapier ◽  
Andreas H. Ehrensberger ◽  
Elodie Darbo ◽  
Bradley R. Cairns ◽  
...  
Keyword(s):  
Experimental System ◽  
Yeast Genome ◽  
Natural Material ◽  
Trna Genes ◽  
Genomic Context ◽  
Protein Coding ◽  
Genome Wide ◽  
Nucleosome Stability

Chromatin transactions are typically studied in vivo, or in vitro using artificial chromatin lacking the epigenetic complexity of the natural material. Attempting to bridge the gap between these approaches, we established a system for isolating the yeast genome as a library of mono-nucleosomes harboring the natural epigenetic signature, suitable for biochemical manipulation. Combined with deep sequencing, this library was used to investigate the intrinsic stability of individual nucleosomes, and – as proof of principle - the nucleosome preference of the chromatin remodeling complex, RSC. Our data indicate that the natural stability of nucleosomes differs greatly, with nucleosomes on tRNA genes and on promoters of protein-coding genes standing out as intrinsically unstable. Interestingly, RSC shows a distinct preference for nucleosomes derived from regions with a high density of histone variant H2A.Z, and this preference is indeed markedly diminished using nucleosomes from cells lacking H2A.Z. Importantly, the preference for H2A.Z remodeling/nucleosome ejection can also be reconstituted with recombinant nucleosome arrays. Together, our data indicate that, despite being separated from their genomic context, individual nucleosomes can retain their original identity as promoter- or TSS-nucleosomes. Besides shedding new light on nucleosome stability and the chromatin remodeler RSC, the simple experimental system outlined here should be generally applicable to the study of chromatin transactions.

scholarly journals The open targets post-GWAS analysis pipeline

2020 ◽  
Vol 36 (9) ◽  
pp. 2936-2937 ◽  
Author(s):  
Gareth Peat ◽  
William Jones ◽  
Michael Nuhn ◽  
José Carlos Marugán ◽  
William Newell ◽  
...  
Keyword(s):  
Drug Targets ◽  
Gene Expression Regulation ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Protein Coding ◽  
Data Resource ◽  
Coding Regions ◽  
Genome Wide ◽  
Causal Genes ◽  
Interactive Data

Abstract Motivation Genome-wide association studies (GWAS) are a powerful method to detect even weak associations between variants and phenotypes; however, many of the identified associated variants are in non-coding regions, and presumably influence gene expression regulation. Identifying potential drug targets, i.e. causal protein-coding genes, therefore, requires crossing the genetics results with functional data. Results We present a novel data integration pipeline that analyses GWAS results in the light of experimental epigenetic and cis-regulatory datasets, such as ChIP-Seq, Promoter-Capture Hi-C or eQTL, and presents them in a single report, which can be used for inferring likely causal genes. This pipeline was then fed into an interactive data resource. Availability and implementation The analysis code is available at www.github.com/Ensembl/postgap and the interactive data browser at postgwas.opentargets.io.

scholarly journals Promoter Methylation of PRKCB, ADAMTS12, and NAALAD2 Is Specific to Prostate Cancer and Predicts Biochemical Disease Recurrence

2021 ◽  
Vol 22 (11) ◽  
pp. 6091
Author(s):  
Kristina Daniunaite ◽  
Arnas Bakavicius ◽  
Kristina Zukauskaite ◽  
Ieva Rauluseviciute ◽  
Juozas Rimantas Lazutka ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Practice ◽  
Promoter Methylation ◽  
Disease Recurrence ◽  
The Cancer Genome Atlas ◽  
Cancer Dataset ◽  
Protein Coding ◽  
Diagnosis And Prognosis ◽  
Genome Wide ◽  
Cancer Genome Atlas

The molecular diversity of prostate cancer (PCa) has been demonstrated by recent genome-wide studies, proposing a significant number of different molecular markers. However, only a few of them have been transferred into clinical practice so far. The present study aimed to identify and validate novel DNA methylation biomarkers for PCa diagnosis and prognosis. Microarray-based methylome data of well-characterized cancerous and noncancerous prostate tissue (NPT) pairs was used for the initial screening. Ten protein-coding genes were selected for validation in a set of 151 PCa, 51 NPT, as well as 17 benign prostatic hyperplasia samples. The Prostate Cancer Dataset (PRAD) of The Cancer Genome Atlas (TCGA) was utilized for independent validation of our findings. Methylation frequencies of ADAMTS12, CCDC181, FILIP1L, NAALAD2, PRKCB, and ZMIZ1 were up to 91% in our study. PCa specific methylation of ADAMTS12, CCDC181, NAALAD2, and PRKCB was demonstrated by qualitative and quantitative means (all p < 0.05). In agreement with PRAD, promoter methylation of these four genes was associated with the transcript down-regulation in the Lithuanian cohort (all p < 0.05). Methylation of ADAMTS12, NAALAD2, and PRKCB was independently predictive for biochemical disease recurrence, while NAALAD2 and PRKCB increased the prognostic power of multivariate models (all p < 0.01). The present study identified methylation of ADAMTS12, NAALAD2, and PRKCB as novel diagnostic and prognostic PCa biomarkers that might guide treatment decisions in clinical practice.

scholarly journals Alu RNA Modulates the Expression of Cell Cycle Genes in Human Fibroblasts

2019 ◽  
Vol 20 (13) ◽  
pp. 3315 ◽  
Author(s):  
Simona Cantarella ◽  
Davide Carnevali ◽  
Marco Morselli ◽  
Anastasia Conti ◽  
Matteo Pellegrini ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Human Fibroblasts ◽  
Rna Polymerase Iii ◽  
Protein Coding ◽  
Non Coding Rna ◽  
Genome Wide ◽  
Hela Cell Lines ◽  
Significant Enrichment ◽  
Alu Rna

Alu retroelements, whose retrotransposition requires prior transcription by RNA polymerase III to generate Alu RNAs, represent the most numerous non-coding RNA (ncRNA) gene family in the human genome. Alu transcription is generally kept to extremely low levels by tight epigenetic silencing, but it has been reported to increase under different types of cell perturbation, such as viral infection and cancer. Alu RNAs, being able to act as gene expression modulators, may be directly involved in the mechanisms determining cellular behavior in such perturbed states. To directly address the regulatory potential of Alu RNAs, we generated IMR90 fibroblasts and HeLa cell lines stably overexpressing two slightly different Alu RNAs, and analyzed genome-wide the expression changes of protein-coding genes through RNA-sequencing. Among the genes that were upregulated or downregulated in response to Alu overexpression in IMR90, but not in HeLa cells, we found a highly significant enrichment of pathways involved in cell cycle progression and mitotic entry. Accordingly, Alu overexpression was found to promote transition from G1 to S phase, as revealed by flow cytometry. Therefore, increased Alu RNA may contribute to sustained cell proliferation, which is an important factor of cancer development and progression.

scholarly journals A Nonsense Variant in Hephaestin Like 1 (HEPHL1) Is Responsible for Congenital Hypotrichosis in Belted Galloway Cattle

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 643
Author(s):  
Thibaud Kuca ◽  
Brandy M. Marron ◽  
Joana G. P. Jacinto ◽  
Julia M. Paris ◽  
Christian Gerspach ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Homozygosity Mapping ◽  
Mendelian Inheritance ◽  
Large Animal Model ◽  
Large Animal ◽  
Loss Of Function ◽  
Protein Coding ◽  
Positional Candidate ◽  
Genome Wide ◽  
A Genome

Genodermatosis such as hair disorders mostly follow a monogenic mode of inheritance. Congenital hypotrichosis (HY) belong to this group of disorders and is characterized by abnormally reduced hair since birth. The purpose of this study was to characterize the clinical phenotype of a breed-specific non-syndromic form of HY in Belted Galloway cattle and to identify the causative genetic variant for this recessive disorder. An affected calf born in Switzerland presented with multiple small to large areas of alopecia on the limbs and on the dorsal part of the head, neck, and back. A genome-wide association study using Swiss and US Belted Galloway cattle encompassing 12 cases and 61 controls revealed an association signal on chromosome 29. Homozygosity mapping in a subset of cases refined the HY locus to a 1.5 Mb critical interval and subsequent Sanger sequencing of protein-coding exons of positional candidate genes revealed a stop gain variant in the HEPHL1 gene that encodes a multi-copper ferroxidase protein so-called hephaestin like 1 (c.1684A>T; p.Lys562*). A perfect concordance between the homozygous presence of this most likely pathogenic loss-of-function variant and the HY phenotype was found. Genotyping of more than 700 purebred Swiss and US Belted Galloway cattle showed the global spread of the mutation. This study provides a molecular test that will permit the avoidance of risk matings by systematic genotyping of relevant breeding animals. This rare recessive HEPHL1-related form of hypotrichosis provides a novel large animal model for similar human conditions. The results have been incorporated in the Online Mendelian Inheritance in Animals (OMIA) database (OMIA 002230-9913).

scholarly journals EagleImp: Fast and Accurate Genome-wide Phasing and Imputation in a Single Tool

2022 ◽  
Author(s):  
Lars Wienbrandt ◽  
David Ellinghaus
Keyword(s):  
Memory Management ◽  
Imputation Accuracy ◽  
Simulated Data ◽  
Genotype Imputation ◽  
Whole Genome Sequencing Data ◽  
Common Variants ◽  
Sequencing Data ◽  
1000 Genomes ◽  
Genome Wide ◽  
Reference Genomes

Background: Reference-based phasing and genotype imputation algorithms have been developed with sublinear theoretical runtime behaviour, but runtimes are still high in practice when large genome-wide reference datasets are used. Methods: We developed EagleImp, a software with algorithmic and technical improvements and new features for accurate and accelerated phasing and imputation in a single tool. Results: We compared accuracy and runtime of EagleImp with Eagle2, PBWT and prominent imputation servers using whole-genome sequencing data from the 1000 Genomes Project, the Haplotype Reference Consortium and simulated data with more than 1 million reference genomes. EagleImp is 2 to 10 times faster (depending on the single or multiprocessor configuration selected) than Eagle2/PBWT, with the same or better phasing and imputation quality in all tested scenarios. For common variants investigated in typical GWAS studies, EagleImp provides same or higher imputation accuracy than the Sanger Imputation Service, Michigan Imputation Server and the newly developed TOPMed Imputation Server, despite larger (not publicly available) reference panels. It has many new features, including automated chromosome splitting and memory management at runtime to avoid job aborts, fast reading and writing of large files, and various user-configurable algorithm and output options. Conclusions: Due to the technical optimisations, EagleImp can perform fast and accurate reference-based phasing and imputation for future very large reference panels with more than 1 million genomes. EagleImp is freely available for download from https://github.com/ikmb/eagleimp.

scholarly journals Identification of high-efficiency 3′GG gRNA motifs in indexed FASTA files with ngg2

2015 ◽  
Vol 1 ◽  
pp. e33 ◽  
Author(s):  
Elisha D. Roberson
Keyword(s):  
High Efficiency ◽  
Homo Sapiens ◽  
Model Organisms ◽  
Proof Of Concept ◽  
Protein Coding ◽  
C Elegans ◽  
Protein Coding Genes ◽  
Starting Point ◽  
Command Line Tool ◽  
Reference Genomes

CRISPR/Cas9 is emerging as one of the most-used methods of genome modification in organisms ranging from bacteria to human cells. However, the efficiency of editing varies tremendously site-to-site. A recent report identified a novel motif, called the 3′GG motif, which substantially increases the efficiency of editing at all sites tested inC. elegans. Furthermore, they highlighted that previously published gRNAs with high editing efficiency also had this motif. I designed a Python command-line tool, ngg2, to identify 3′GG gRNA sites from indexed FASTA files. As a proof-of-concept, I screened for these motifs in six model genomes:Saccharomyces cerevisiae,Caenorhabditis elegans,Drosophila melanogaster,Danio rerio,Mus musculus, andHomo sapiens. I also scanned the genomes of pig (Sus scrofa) and African elephant (Loxodonta africana) to demonstrate the utility in non-model organisms. I identified more than 60 million single match 3′GG motifs in these genomes. Greater than 61% of all protein coding genes in the reference genomes had at least one unique 3′GG gRNA site overlapping an exon. In particular, more than 96% of mouse and 93% of human protein coding genes have at least one unique, overlapping 3′GG gRNA. These identified sites can be used as a starting point in gRNA selection, and the ngg2 tool provides an important ability to identify 3′GG editing sites in any species with an available genome sequence.

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