scholarly journals Framework for quality assessment of whole genome, cancer sequences

2017 ◽  
Author(s):  
Justin P. Whalley ◽  
Ivo Buchhalter ◽  
Esther Rheinbay ◽  
Keiran M. Raine ◽  
Kortine Kleinheinz ◽  
...  
Keyword(s):  
Quality Measures ◽  
Poor Quality ◽  
Whole Genome ◽  
Genome Sequences ◽  
International Cancer Genome Consortium ◽  
Whole Genomes ◽  
Sequencing Quality ◽  
Genome Consortium ◽  
Pan Cancer

AbstractWorking with cancer whole genomes sequenced over a period of many years in different sequencing centres requires a validated framework to compare the quality of these sequences. The Pan-Cancer Analysis of Whole Genomes (PCAWG) of the International Cancer Genome Consortium (ICGC), a project a cohort of over 2800 donors provided us with the challenge of assessing the quality of the genome sequences. A non-redundant set of five quality control (QC) measurements were assembled and used to establish a star rating system. These QC measures reflect known differences in sequencing protocol and provide a guide to downstream analyses of these whole genome sequences. The resulting QC measures also allowed for exclusion samples of poor quality, providing researchers within PCAWG, and when the data is released for other researchers, a good idea of the sequencing quality. For a researcher wishing to apply the QC measures for their data we provide a Docker Container of the software used to calculate them. We believe that this is an effective framework of quality measures for whole genome, cancer sequences, which will be a useful addition to analytical pipelines, as it has to the PCAWG project.

scholarly journals Framework for quality assessment of whole genome cancer sequences

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Justin P. Whalley ◽  
Ivo Buchhalter ◽  
Esther Rheinbay ◽  
Keiran M. Raine ◽  
Miranda D. Stobbe ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Quality Measures ◽  
Poor Quality ◽  
Rating System ◽  
Test Case ◽  
Whole Genome ◽  
Whole Genomes ◽  
Cancer Genomes ◽  
Pan Cancer

Abstract Bringing together cancer genomes from different projects increases power and allows the investigation of pan-cancer, molecular mechanisms. However, working with whole genomes sequenced over several years in different sequencing centres requires a framework to compare the quality of these sequences. We used the Pan-Cancer Analysis of Whole Genomes cohort as a test case to construct such a framework. This cohort contains whole cancer genomes of 2832 donors from 18 sequencing centres. We developed a non-redundant set of five quality control (QC) measurements to establish a star rating system. These QC measures reflect known differences in sequencing protocol and provide a guide to downstream analyses and allow for exclusion of samples of poor quality. We have found that this is an effective framework of quality measures. The implementation of the framework is available at: https://dockstore.org/containers/quay.io/jwerner_dkfz/pancanqc:1.2.2.

Oocyte IVM or vitrification significantly impairs DNA methylation patterns in blastocysts as analysed by single-cell whole-genome methylation sequencing

2020 ◽  
Vol 32 (7) ◽  
pp. 676
Author(s):  
Ya-Han Zhao ◽  
Jing-Jing Wang ◽  
Pei-Pei Zhang ◽  
Hai-Sheng Hao ◽  
Yun-Wei Pang ◽  
...  
Keyword(s):  
Single Cell ◽  
Protein Phosphatase ◽  
Poor Quality ◽  
Protein Phosphatase 1 ◽  
Regulatory Subunit ◽  
Whole Genome ◽  
Genome Methylation ◽  
Sequencing Technique ◽  
Methylation Patterns

To explore the mechanisms leading to the poor quality of IVF blastocysts, the single-cell whole-genome methylation sequencing technique was used in this study to analyse the methylation patterns of bovine blastocysts derived from invivo, fresh (IVF) or vitrified (V_IVF) oocytes. Genome methylation levels of blastocysts in the IVF and V_IVF groups were significantly lower than those of the invivo group (P<0.05). In all, 1149 differentially methylated regions (DMRs) were identified between the IVF and invivo groups, 1578 DMRs were identified between the V_IVF and invivo groups and 151 DMRs were identified between the V_IVF and IVF groups. For imprinted genes, methylation levels of insulin-like growth factor 2 receptor (IGF2R) and protein phosphatase 1 regulatory subunit 9A (PPP1R9A) were lower in the IVF and V_IVF groups than in the invivo group, and the methylation level of paternally expressed 3 (PEG3) was lower in the V_IVF group than in the IVF and invivo groups. Genes with DMRs between the IVF and invivo and the V_IVF and IVF groups were primarily enriched in oocyte maturation pathways, whereas DMRs between the V_IVF and invivo groups were enriched in fertilisation and vitrification-vulnerable pathways. The results of this study indicate that differences in the methylation of critical DMRs may contribute to the differences in quality between invitro- and invivo-derived embryos.

scholarly journals Complete genome sequence and analysis of nine Egyptian females with clinical information from different geographic regions in Egypt

2020 ◽  
Author(s):  
Mahmoud ElHefnawi ◽  
Elsayed Hegazy ◽  
Asmaa ElFiky ◽  
Yeonsu Jeon ◽  
Sungwon Jeon ◽  
...  
Keyword(s):  
Middle Eastern ◽  
Clinical Information ◽  
Human Migration ◽  
Progressive External Ophthalmoplegia ◽  
Whole Genome ◽  
Mtdna Mutation ◽  
Genome Sequences ◽  
Whole Genomes ◽  
Genetic And Environmental Factors ◽  
Genomic Resource

AbstractEgyptians are at a crossroad between Africa and Eurasia, providing useful genomic resources for analyzing both genetic and environmental factors for future personalized medicine. Two personal Egyptian whole genomes have been published previously and here nine female whole genome sequences with clinical information have been added to expand the genomic resource of Egyptian personal genomes. Here we report the analysis of whole genomes of nine Egyptian females from different regions using Illumina short-read sequencers. At 30x sequencing coverage, we identified 12 SNPs that were shared in most of the subjects associated with obesity which are concordant with their clinical diagnosis. Also, we found mtDNA mutation A4282G is common in all the samples and this is associated with chronic progressive external ophthalmoplegia (CPEO). Haplogroup and Admixture analyses revealed that most Egyptian samples are close to the other north Mediterranean, Middle Eastern, and European, respectively, possibly reflecting the into-Africa influx of human migration. In conclusion, we present whole-genome sequences of nine Egyptian females with personal clinical information that cover the diverse regions of Egypt. Although limited in sample size, the whole genomes data provides possible geno-phenotype candidate markers that are relevant to the region’s diseases.

scholarly journals Retention and Loss of Amino Acid Biosynthetic Pathways Based on Analysis of Whole-Genome Sequences

2006 ◽  
Vol 5 (2) ◽  
pp. 272-276 ◽  
Author(s):  
Samuel H. Payne ◽  
William F. Loomis
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Minimal Medium ◽  
Whole Genome ◽  
Biosynthetic Pathways ◽  
Genome Sequences ◽  
Whole Genomes ◽  
Complete Genomes ◽  
Computational Analyses

ABSTRACT Plants and fungi can synthesize each of the 20 amino acids by using biosynthetic pathways inherited from their bacterial ancestors. However, the ability to synthesize nine amino acids (Phe, Trp, Ile, Leu, Val, Lys, His, Thr, and Met) was lost in a wide variety of eukaryotes that evolved the ability to feed on other organisms. Since the biosynthetic pathways and their respective enzymes are well characterized, orthologs can be recognized in whole genomes to understand when in evolution pathways were lost. The pattern of pathway loss and retention was analyzed in the complete genomes of three early-diverging protist parasites, the amoeba Dictyostelium, and six animals. The nine pathways were lost independently in animals, Dictyostelium, Leishmania, Plasmodium, and Cryptosporidium. Seven additional pathways appear to have been lost in one or another parasite, demonstrating that they are dispensable in a nutrition-rich environment. Our predictions of pathways retained and pathways lost based on computational analyses of whole genomes are validated by minimal-medium studies with mammals, fish, worms, and Dictyostelium. The apparent selective advantages of retaining biosynthetic capabilities for amino acids available in the diet are considered.

scholarly journals Whole genome and RNA sequencing of 1,220 cancers reveals hundreds of genes deregulated by rearrangement of cis-regulatory elements

2017 ◽  
Author(s):  
Yiqun Zhang ◽  
Fengju Chen ◽  
Nuno A. Fonseca ◽  
Yao He ◽  
Masashi Fujita ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Promoter ◽  
Regulatory Elements ◽  
Whole Genome ◽  
Expression Data ◽  
Structural Variants ◽  
Altered Expression ◽  
Genes Expression ◽  
Whole Genomes ◽  
Pan Cancer

AbstractUsing a dataset of somatic Structural Variants (SVs) in cancers from 2658 patients—1220 with corresponding gene expression data—we identified hundreds of genes for which the nearby presence (within 100kb) of an SV breakpoint was associated with altered expression. For the vast majority of these genes, expression was increased rather than decreased with corresponding SV event. Well-known up-regulated cancer-associated genes impacted by this phenomenon included TERT, MDM2, CDK4, ERBB2, CD274, PDCD1LG2, and IGF2. SVs upstream of TERT involved ~3% of cancer cases and were most frequent in liver-biliary, melanoma, sarcoma, stomach, and kidney cancers. SVs associated with up-regulation of PD1 and PDL1 genes involved ~1% of non-amplified cases. For many genes, SVs were significantly associated with either increased numbers or greater proximity of enhancer regulatory elements near the gene. DNA methylation near the gene promoter was often increased with nearby SV breakpoint, which may involve inactivation of repressor elements.AbbreviationsPCAWGthe Pan-Cancer Analysis of Whole Genomes projectSVStructural Variant

scholarly journals Verification of genetic engineering in yeasts with nanopore whole genome sequencing

2020 ◽  
Author(s):  
Joseph H. Collins ◽  
Kevin W. Keating ◽  
Trent R. Jones ◽  
Shravani Balaji ◽  
Celeste B. Marsan ◽  
...  
Keyword(s):  
Quality Control ◽  
Synthetic Biology ◽  
Genome Assembly ◽  
Whole Genome ◽  
Sequencing Data ◽  
Genome Sequences ◽  
Yeast Strains ◽  
Whole Genomes ◽  
Before And After ◽  
Integrated Pathway

ABSTRACTYeast genomes can be assembled from sequencing data, but genome integrations and episomal plasmids often fail to be resolved with accuracy, completeness, and contiguity. Resolution of these features is critical for many synthetic biology applications, including strain quality control and identifying engineering in unknown samples. Here, we report an integrated workflow, named Prymetime, that uses sequencing reads from inexpensive NGS platforms, assembly and error correction software, and a list of synthetic biology parts to achieve accurate whole genome sequences of yeasts with engineering annotated. To build the workflow, we first determined which sequencing methods and software packages returned an accurate, complete, and contiguous genome of an engineered S. cerevisiae strain with two similar plasmids and an integrated pathway. We then developed a sequence feature annotation step that labels synthetic biology parts from a standard list of yeast engineering sequences or from a custom sequence list. We validated the workflow by sequencing a collection of 15 engineered yeasts built from different parent S. cerevisiae and nonconventional yeast strains. We show that each integrated pathway and episomal plasmid can be correctly assembled and annotated, even in strains that have part repeats and multiple similar plasmids. Interestingly, Prymetime was able to identify deletions and unintended integrations that were subsequently confirmed by other methods. Furthermore, the whole genomes are accurate, complete, and contiguous. To illustrate this clearly, we used a publicly available S. cerevisiae CEN.PK113 reference genome and the accompanying reads to show that a Prymetime genome assembly is equivalent to the reference using several standard metrics. Finally, we used Prymetime to resequence the nonconventional yeasts Y. lipolytica Po1f and K. phaffii CBS 7435, producing an improved genome assembly for each strain. Thus, our workflow can achieve accurate, complete, and contiguous whole genome sequences of yeast strains before and after engineering. Therefore, Prymetime enables NGS-based strain quality control through assembly and identification of engineering features.

scholarly journals OligoPVP: Phenotype-driven analysis of individual genomic information to prioritize oligogenic disease variants

2018 ◽  
Author(s):  
Imane Boudellioua ◽  
Maxat Kulmanov ◽  
Paul N Schofield ◽  
Georgios V Gkoutos ◽  
Robert Hoehndorf
Keyword(s):  
Detection Methods ◽  
Whole Genome ◽  
Variant Prioritization ◽  
Genome Sequences ◽  
Mendelian Disorders ◽  
Mendelian Diseases ◽  
Whole Exome ◽  
Whole Genomes ◽  
Improved Performance ◽  
Selection Of

ABSTRACTPurposeAn increasing number of Mendelian disorders have been identified for which two or more variants in one or more genes are required to cause the disease, or significantly modify its severity or phenotype. It is difficult to discover such interactions using existing approaches. The purpose of our work is to develop and evaluate a system that can identify combinations of variants underlying oligogenic diseases in individual whole exome or whole genome sequences.MethodsInformation that links patient phenotypes to databases of gene–phenotype associations observed in clinical research can provide useful information and improve variant prioritization for Mendelian diseases. Additionally, background knowledge about interactions between genes can be utilized to guide and restrict the selection of candidate disease modules.ResultsWe developed OligoPVP, an algorithm that can be used to identify variants in oligogenic diseases and their interactions, using whole exome or whole genome sequences together with patient phenotypes as input. We demonstrate that OligoPVP has significantly improved performance when compared to state of the art pathogenicity detection methods.ConclusionsOur results show that OligoPVP can efficiently detect oligogenic interactions using a phenotype-driven approach and identify etiologically important variants in whole genomes.

An experience of performing spirometry by trained general practitioners

2020 ◽  
pp. 34-36
Author(s):  
M. A. Pokhaznikova ◽  
E. A. Andreeva ◽  
O. Yu. Kuznetsova
Keyword(s):  
General Practitioners ◽  
Quality Criteria ◽  
Poor Quality ◽  
Male Gender ◽  
Study Research ◽  
The Poor ◽  
Quality Of Research ◽  
Forced Expiratory Maneuver ◽  
Maximal Effort

The article discusses the experience of teaching and conducting spirometry of general practitioners as part of the RESPECT study (RESearch on the PrEvalence and the diagnosis of COPD and its Tobacco-related aetiology). A total of 33 trained in spirometry general practitioners performed a study of 3119 patients. Quality criteria met 84.1% of spirometric studies. The analysis of the most common mistakes made by doctors during the forced expiratory maneuver is included. The most frequent errors were expiration exhalation of less than 6s (54%), non-maximal effort throughout the test and lack of reproducibility (11.3%). Independent predictors of poor spirogram quality were male gender, obstruction (FEV1 /FVC<0.7), and the center where the study was performed. The number of good-quality spirograms ranged from 96.1% (95% CI 83.2–110.4) to 59.8% (95% CI 49.6–71.4) depending on the center. Subsequently, an analysis of the reasons behind the poor quality of research in individual centers was conducted and the identified shortcomings were eliminated. The poor quality of the spirograms was associated either with the errors of the doctors who undertook the study or with the technical malfunctions of the spirometer.

KUALITAS HIDUP PASIEN STROKE DI POLIKLINIK RAWAT JALAN RUMAH SAKIT SWASTA YOGYAKARTA

2019 ◽  
Vol 7 (3) ◽  
pp. 232-237
Author(s):  
Hana Larasati ◽  
Theresia Titin Marlina
Keyword(s):  
Quality Of Life ◽  
Social Relations ◽  
Hemorrhagic Stroke ◽  
Poor Quality ◽  
Social Dimension ◽  
Stroke Patients ◽  
Sampling System ◽  
Post Stroke ◽  
Psychological Dimension

Background: stroke is a disorder of nervous system function that occurs suddenly and is caused by brain bleeding disorders that can affect the quality of life physical dimensions, social dimensions, psychological dimensions, environmental dimensions. Based on the result of Lumbu study (2015) the number of samples were 71 people collected data using the (WHOQOL-BREF). There were 56 people (78,9%) had the poor quality of life of post stroke. The mean of post-stroke quality of life domain was physical domain (45,27%), psychological domain (49,87%), social relations domain (48,15%) and environmental domain (50.01%). Objective: the purpose of the study was know the quality of life of the stroke patients in Outpatient Polyclinic of Private Hospital in Yogyakarta. Methods: used descriptive quantitative by using questionnaire test of purposive sampling system based on patients who have been affected of ischemic or hemorrhagic stroke before, number 30 respondents. Result: quality of life of stroke patient of medium physical dimension (67%), psychological dimension (71%), social dimension (67%), dimension good environment (63%). Conclusion: the quality of life of stroke patients of physical dimension, psychological dimension, and moderate social dimension, while the quality of life of stroke patients were good environmental dimension.   Keywords: Hemorrhagic stroke, ischemic stroke, quality of life

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