ContaTester: Fast cross-contamination estimation and identification for large human sequencing cohorts

AbstractBackgroundInterest in genomic medicine for human health studies and clinical applications is rapidly increasing. Clinical applications require contamination-free samples to avoid misleading results and provide a sound basis for diagnosis.ResultsHere we present ContaTester, a tool which requires only allele balance information gathered from a VCF file to detect cross-contamination in germline human DNA samples. Based on a regression model of allele balance distribution, ContaTester allows fast checking of contamination levels for single samples or large cohorts (less than two minutes per sample). We demonstrate the efficiency of ContaTester using experimental validations: ContaTester shows similar results to methods requiring alignment data but with a significantly reduced storage footprint and less computation time. Additionally, for contamination levels above 5%, ContaTester can identify contaminants across a cohort, providing important clues for troubleshooting and quality assessment.ConclusionsContaTester estimates contamination levels from VCF files generated from whole genome sequencing normal sample and provides reliable contaminant identification for cohorts or experimental batches.

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Animal feeding stuffs: Methods of sampling and analysis - Screening and determination of authorized coccidiostats at additive and 1 % and 3 % cross-contamination levels, and of non-registered coccidiostats and of one antibiotic at sub-additive levels, in compound feed with High Performance Liquid Chromatography - Tandem Mass Spectrometry detection (LC-MS/MS)

10.3403/30348301 ◽

2019 ◽

Keyword(s):

Mass Spectrometry ◽

High Performance ◽

Tandem Mass ◽

Cross Contamination ◽

Mass Spectrometry Detection ◽

Chromatography Tandem Mass Spectrometry ◽

Liquid Chromatography Tandem Mass ◽

Animal Feeding ◽

Contamination Levels

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Determination of Dimetridazole and Ipronidazole in Feeds at Cross-Contamination Levels

Journal of AOAC INTERNATIONAL ◽

10.1093/jaoac/71.3.474 ◽

1988 ◽

Vol 71 (3) ◽

pp. 474-477 ◽

Cited By ~ 1

Author(s):

Duane D Hughes

Keyword(s):

Thin Layer ◽

Rapid Method ◽

Aqueous Phase ◽

Borate Buffer ◽

Cross Contamination ◽

Chromatographic System ◽

Arsanilic Acid ◽

Contamination Levels ◽

Benzene Extract

Abstract A rapid method for the determination of dimetridazole and ipronidazole in feeds is described. The compounds are extracted from a borate buffer (pH 8.65) with benzene, partitioned into IN HC1, and then partitioned back into benzene from a basic aqueous phase. The benzene extract is concentrated and injected onto a nonpolar (Apiezon L) gas chromatographic column for determination by 63Ni electroncapture detection. Recoveries from feeds of various composition, spiked at 0.2 ppm with both dimetridazole and ipronidazole, ranged from 70 to 115%; for the same feeds spiked at 1 ppm or more, the recoveries were greater than 80%. Carbadox, furazolidone, levamisole, oxytetracycline, chlortetracycline, sulfamethazine, sulfaquinoxaline, arsanilic acid, piperazine, penicillin, and commonly added vitamins and minerals do not interfere. A 2-dimensional thin layer chromatographic system is presented as a means of additional identification.

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Continuing the sequence? Towards an economic evaluation of whole genome sequencing for the diagnosis of rare diseases in Scotland

Journal of Community Genetics ◽

10.1007/s12687-021-00541-4 ◽

2021 ◽

Author(s):

Michael Abbott ◽

Lynda McKenzie ◽

Blanca Viridiana Guizar Moran ◽

Sebastian Heidenreich ◽

Rodolfo Hernández ◽

...

Keyword(s):

Economic Evaluation ◽

Genetic Testing ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Rare Diseases ◽

Genomic Medicine ◽

Future Research ◽

Clinical Genetics ◽

Whole Genome ◽

Peace Of Mind

AbstractNovel developments in genomic medicine may reduce the length of the diagnostic odyssey for patients with rare diseases. Health providers must thus decide whether to offer genome sequencing for the diagnosis of rare conditions in a routine clinical setting. We estimated the costs of singleton standard genetic testing and trio-based whole genome sequencing (WGS), in the context of the Scottish Genomes Partnership (SGP) study. We also explored what users value about genomic sequencing. Insights from the costing and value assessments will inform a subsequent economic evaluation of genomic medicine in Scotland. An average cost of £1,841 per singleton was estimated for the standard genetic testing pathway, with significant variability between phenotypes. WGS cost £6625 per family trio, but this estimate reflects the use of WGS during the SGP project and large cost savings may be realised if sequencing was scaled up. Patients and families valued (i) the chance of receiving a diagnosis (and the peace of mind and closure that brings); (ii) the information provided by WGS (including implications for family planning and secondary findings); and (iii) contributions to future research. Our costings will be updated to address limitations of the current study for incorporation in budget impact modelling and cost-effectiveness analysis (cost per diagnostic yield). Our insights into the benefits of WGS will guide the development of a discrete choice experiment valuation study. This will inform a user-perspective cost–benefit analysis of genome-wide sequencing, accounting for the broader non-health outcomes. Taken together, our research will inform the long-term strategic development of NHS Scotland clinical genetics testing services, and will be of benefit to others seeking to undertake similar evaluations in different contexts.

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Identifying Aspects of Public Attitudes Toward Whole Genome Sequencing to Inform the Integration of Genomics into Care

Public Health Genomics ◽

10.1159/000515952 ◽

2021 ◽

pp. 1-12

Author(s):

Holly Etchegary ◽

Daryl Pullman ◽

Charlene Simmonds ◽

Zoha Rabie ◽

Proton Rahman

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Online Survey ◽

Public Attitudes ◽

Genetic Counselor ◽

Genomic Medicine ◽

Genomic Data ◽

Whole Genome ◽

The Public ◽

Genomic Test

Introduction: The growth of global sequencing initiatives and commercial genomic test offerings suggests the public will increasingly be confronted with decisions about sequencing. Understanding public attitudes can assist efforts to integrate sequencing into care and inform the development of public education and outreach strategies. Methods: A 48-item online survey was advertised on Facebook in Eastern Canada and hosted on SurveyMonkey in late 2018. The survey measured public interest in whole genome sequencing and attitudes toward various aspects of sequencing using vignettes, scaled, and open-ended items. Results: While interest in sequencing was high, critical attitudes were observed. In particular, items measuring features of patient control and choice regarding genomic data were strongly endorsed by respondents. Majority wanted to specify upfront how their data could be used, retain the ability to withdraw their sample at a later date, sign a written consent form, and speak to a genetic counselor prior to sequencing. Concerns about privacy and unauthorized access to data were frequently observed. Education level was the sociodemographic variable most often related to attitude statements such that those with higher levels of education generally displayed more critical attitudes. Conclusions: Attitudes identified here could be used to inform the development of implementation strategies for genomic medicine. Findings suggest health systems must address patient concerns about privacy, consent practices, and the strong desire to control what happens to their genomic data through public outreach and education. Specific oversight procedures and policies that are clearly communicated to the public will be required.

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Use of Synthetic Oligonucleotides for the Study of Hypervariable Regions of Human DNA and Their Clinical Applications

Immunobiology of HLA ◽

10.1007/978-3-662-39946-0_224 ◽

1989 ◽

pp. 520-521

Author(s):

L. Ugozzoli ◽

P. Briata ◽

C. Delfini ◽

G. Lucarelli ◽

B. Wallace ◽

...

Keyword(s):

Clinical Applications ◽

Hypervariable Regions ◽

Human Dna ◽

Synthetic Oligonucleotides

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6 Translating genomics for clinical benefit

Postgraduate Medical Journal ◽

10.1136/postgradmedj-2019-fpm.6 ◽

2019 ◽

Vol 95 (1130) ◽

pp. 686.3-686

Author(s):

Mark Caulfield

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Genomic Medicine ◽

Health Gain ◽

Annual Review ◽

Whole Genome ◽

Department Of Health ◽

Data Points ◽

Genome Analyses ◽

The Uk

The UK 100,000 Genomes Project has focussed on transforming genomic medicine in the National Health Service using whole genome sequencing in rare disease, cancer and infection. Genomics England partnering with the NHS established 13 Genomic Medicine Centres, the NHS whole genome sequencing centre and the Genomics England Clinical Interpretation Partnership (3337 researchers from 24 countries). We sequenced the 100,000th genome on the 5th December 2019 and completed an initial analysis for participants in July 2019. Alongside these genomes we have assembled a longitudinal life course dataset for research and diagnosis including 2.6 billion clinical data points for the 3000 plus researchers to work on to drive up the value of the genomes for direct healthcare. In parallel we have partnered the NHS to establish one of the world’s most advanced Genomic Medicine Service where we re-evaluated 300,000 genomic tests and upgraded 25% of tests to newer technologies with an annual review. The Department of Health have announced the ambition to undertake 5 million genome analyses over the next 5 years focused on new areas tractable to health gain.

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Patents and Genome-Wide DNA Sequence Analysis: Is it Safe to Go into the Human Genome?

The Journal of Law Medicine & Ethics ◽

10.1111/jlme.12161 ◽

2014 ◽

Vol 42 (S1) ◽

pp. 42-50 ◽

Cited By ~ 6

Author(s):

Robert Cook-Deegan ◽

Subhashini Chandrasekharan

Keyword(s):

Clinical Applications ◽

Patent Infringement ◽

Whole Genome ◽

Whole Genome Analysis ◽

Business Decisions ◽

Gene Patents ◽

Clinical Laboratories ◽

Genome Wide ◽

Human Genes ◽

Genome Analyses

Whether, and to what degree, do patents granted on human genes cast a shadow of uncertainty over genomics and its applications? Will owners of patents on individual genes or clusters of genes sue those performing whole-genome analyses on human samples for patent infringement? These are related questions that have haunted molecular diagnostics companies and services, coloring scientific, clinical, and business decisions. Can the profusion of whole-genome analysis methods proceed without fear of patent infringement liability?Whole-genome sequencing (WGS) is proceeding apace. Academic centers have been performing whole-genome and -exome sequencing (WES) in research for at least five years, and academic clinical laboratories with national reach have been doing sequencing for clinical applications for almost as long. Companies have also been offering WGS and WES as a clinical service for a few years now. So far as we know, no one has been sued for infringement of “gene patents” for performing WGS.

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Analytical validation of whole exome and whole genome sequencing for clinical applications

BMC Medical Genomics ◽

10.1186/1755-8794-7-20 ◽

2014 ◽

Vol 7 (1) ◽

Cited By ~ 73

Author(s):

Michael D Linderman ◽

Tracy Brandt ◽

Lisa Edelmann ◽

Omar Jabado ◽

Yumi Kasai ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Clinical Applications ◽

Whole Genome ◽

Analytical Validation ◽

Whole Exome

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A Clinical Measure for the Assessment of Problem Solving in Brain-Injured Adults

American Journal of Speech-Language Pathology ◽

10.1044/1058-0360(2003/079) ◽

2003 ◽

Vol 12 (3) ◽

pp. 333-348 ◽

Cited By ~ 9

Author(s):

Robert C. Marshall ◽

Colleen M. Karow ◽

Claudia A. Morelli ◽

Kristen King Iden ◽

Judith Dixon

Keyword(s):

Problem Solving ◽

Rapid Assessment ◽

Clinical Applications ◽

Normal Sample ◽

Clinical Test ◽

Problem Solving Skills ◽

Semantic Categories ◽

Brain Injured ◽

Verbal Problem ◽

Traumatically Brain Injured

Rapid Assessment of Problem Solving (RAPS) is a clinical test of verbal problem-solving skills for brain-injured persons. This modification of F. A. Mosher and J. R. Hornsby’s (1966) Twenty Questions Test (20Q) reduces the memory demands of the test for brain-injured clients. This article provides background on the 20Q Test and modifications made for RAPS. It describes RAPS materials, administration, and scoring procedures and reports RAPS results for 70 normal participants. Normal participants solved RAPS problems with an average of 5 questions. Questions were predominantly constraint seeking and focused on semantic categories or features. Normal participants also reflected substantial variability in their performance on RAPS. This appeared to be related to 2 metacognitive abilities associated with problem solving, planning, and shifting set. The performance of 3 chronic traumatically brain injured individuals is also described and compared to the normal sample to illustrate clinical applications of RAPS.

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