18 results on '"Woon, Mark"'
Search Results
2. Phased whole-genome genetic risk in a family quartet using a major allele reference sequence.
- Author
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Dewey, Frederick E, Chen, Rong, Cordero, Sergio P, Ormond, Kelly E, Caleshu, Colleen, Karczewski, Konrad J, Whirl-Carrillo, Michelle, Wheeler, Matthew T, Dudley, Joel T, Byrnes, Jake K, Cornejo, Omar E, Knowles, Joshua W, Woon, Mark, Sangkuhl, Katrin, Gong, Li, Thorn, Caroline F, Hebert, Joan M, Capriotti, Emidio, David, Sean P, Pavlovic, Aleksandra, West, Anne, Thakuria, Joseph V, Ball, Madeleine P, Zaranek, Alexander W, Rehm, Heidi L, Church, George M, West, John S, Bustamante, Carlos D, Snyder, Michael, Altman, Russ B, Klein, Teri E, Butte, Atul J, and Ashley, Euan A
- Subjects
Humans ,Thrombophilia ,Genetic Predisposition to Disease ,Risk Assessment ,Pedigree ,Sequence Alignment ,Sequence Analysis ,DNA ,DNA Mutational Analysis ,Base Sequence ,Genotype ,Haplotypes ,Alleles ,Genes ,Synthetic ,Genome ,Human ,Reference Standards ,Female ,Male ,Genetic Variation ,Genome-Wide Association Study ,Biotechnology ,Genetics ,Human Genome ,2.1 Biological and endogenous factors ,Generic health relevance ,Developmental Biology - Abstract
Whole-genome sequencing harbors unprecedented potential for characterization of individual and family genetic variation. Here, we develop a novel synthetic human reference sequence that is ethnically concordant and use it for the analysis of genomes from a nuclear family with history of familial thrombophilia. We demonstrate that the use of the major allele reference sequence results in improved genotype accuracy for disease-associated variant loci. We infer recombination sites to the lowest median resolution demonstrated to date (< 1,000 base pairs). We use family inheritance state analysis to control sequencing error and inform family-wide haplotype phasing, allowing quantification of genome-wide compound heterozygosity. We develop a sequence-based methodology for Human Leukocyte Antigen typing that contributes to disease risk prediction. Finally, we advance methods for analysis of disease and pharmacogenomic risk across the coding and non-coding genome that incorporate phased variant data. We show these methods are capable of identifying multigenic risk for inherited thrombophilia and informing the appropriate pharmacological therapy. These ethnicity-specific, family-based approaches to interpretation of genetic variation are emblematic of the next generation of genetic risk assessment using whole-genome sequencing.
- Published
- 2011
3. P662: Estimating UK Biobank population-specific PGx allele and phenotype frequencies using PharmCAT
- Author
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Sangkuhl, Katrin, primary, Whaley, Ryan, additional, Woon, Mark, additional, Keat, Karl, additional, Gong, Li, additional, Whirl-Carrillo, Michelle, additional, Ritchie, Marylyn, additional, and Klein, Teri, additional
- Published
- 2023
- Full Text
- View/download PDF
4. How to Run the Pharmacogenomics Clinical Annotation Tool ( PharmCAT )
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Li, Binglan, primary, Sangkuhl, Katrin, additional, Keat, Karl, additional, Whaley, Ryan M., additional, Woon, Mark, additional, Verma, Shefali, additional, Dudek, Scott, additional, Tuteja, Sony, additional, Verma, Anurag, additional, Whirl‐Carrillo, Michelle, additional, Ritchie, Marylyn D., additional, and Klein, Teri E., additional
- Published
- 2022
- Full Text
- View/download PDF
5. How to Run the Pharmacogenomics Clinical Annotation Tool (PharmCAT).
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Li, Binglan, Sangkuhl, Katrin, Keat, Karl, Whaley, Ryan M., Woon, Mark, Verma, Shefali, Dudek, Scott, Tuteja, Sony, Verma, Anurag, Whirl‐Carrillo, Michelle, Ritchie, Marylyn D., and Klein, Teri E.
- Subjects
PHARMACOGENOMICS ,CLINICAL decision support systems ,INDIVIDUALIZED medicine ,BUSINESS insurance ,ANNOTATIONS ,CONSORTIA - Abstract
Pharmacogenomics (PGx) investigates the genetic influence on drug response and is an integral part of precision medicine. While PGx testing is becoming more common in clinical practice and may be reimbursed by Medicare/Medicaid and commercial insurance, interpreting PGx testing results for clinical decision support is still a challenge. The Pharmacogenomics Clinical Annotation Tool (PharmCAT) has been designed to tackle the need for transparent, automatic interpretations of patient genetic data. PharmCAT incorporates a patient's genotypes, annotates PGx information (allele, genotype, and phenotype), and generates a report with PGx guideline recommendations from the Clinical Pharmacogenetics Implementation Consortium (CPIC) and/or the Dutch Pharmacogenetics Working Group (DPWG). PharmCAT has introduced new features in the last 2 years, including a variant call format (VCF) Preprocessor, the inclusion of DPWG guidelines, and functionalities for PGx research. For example, researchers can use the VCF Preprocessor to prepare biobank‐scale data for PharmCAT. In addition, PharmCAT enables the assessment of novel partial and combination alleles that are composed of known PGx variants and can call CYP2D6 genotypes based on single and deletions in the input VCF file. This tutorial provides materials and detailed step‐by‐step instructions for how to use PharmCAT in a versatile way that can be tailored to users' individual needs. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
6. Clinical assessment incorporating a personal genome
- Author
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Ashley, Euan A, Butte, Atul J, Wheeler, Matthew T, Chen, Rong, Klein, Teri E, Dewey, Frederick E, Dudley, Joel T, Ormond, Kelly E, Pavlovic, Aleksandra, Morgan, Alexander A, Pushkarev, Dmitry, Neff, Norma F, Hudgins, Louanne, Gong, Li, Hodges, Laura M, Berlin, Dorit S, Thorn, Caroline F, Sangkuhl, Katrin, Hebert, Joan M, Woon, Mark, Sagreiya, Hersh, Whaley, Ryan, Knowles, Joshua W, Chou, Michael F, Thakuria, Joseph V, Rosenbaum, Abraham M, Zaranek, Alexander Wait, Church, George M, Greely, Henry T, Quake, Stephen R, and Altman, Russ B
- Published
- 2010
- Full Text
- View/download PDF
7. PGxMine: Text mining for curation of PharmGKB
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Lever, Jake, primary, Barbarino, Julia M., additional, Gong, Li, additional, Huddart, Rachel, additional, Sangkuhl, Katrin, additional, Whaley, Ryan, additional, Whirl-Carrillo, Michelle, additional, Woon, Mark, additional, Klein, Teri E., additional, and Altman, Russ B., additional
- Published
- 2019
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- View/download PDF
8. The Phenotype and Genotype Experiment Object Model (PaGE-OM): A Robust Data Structure for Information Related to DNA Variation
- Author
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Brookes, Anthony J., Lehvaslaiho, Heikki, Muilu, Juha, Shigemoto, Yasumasa, Oroguchi, Takashige, Tomiki, Takeshi, Mukaiyama, Atsuhiro, Konagaya, Akihiko, Kojima, Toshio, Inoue, Ituro, Kuroda, Masako, Mizushima, Hiroshi, Thorisson, Gudmundur A., Dash, Debasis, Rajeevan, Haseena, Darlison, Matthew W., Woon, Mark, Fredman, David, Smith, Albert V., Senger, Martin, Naito, Kimitoshi, and Sugawara, Hideaki
- Published
- 2009
- Full Text
- View/download PDF
9. The pharmacogenetics and pharmacogenomics knowledge base: accentuating the knowledge
- Author
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Hernandez-Boussard, Tina, Whirl-Carrillo, Michelle, Hebert, Joan M., Gong, Li, Owen, Ryan, Gong, Mei, Gor, Winston, Liu, Feng, Truong, Chuong, Whaley, Ryan, Woon, Mark, Zhou, Tina, Altman, Russ B., and Klein, Teri E.
- Published
- 2008
10. Pharmacogenomics Clinical Annotation Tool (Pharm CAT )
- Author
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Sangkuhl, Katrin, primary, Whirl‐Carrillo, Michelle, additional, Whaley, Ryan M., additional, Woon, Mark, additional, Lavertu, Adam, additional, Altman, Russ B., additional, Carter, Lester, additional, Verma, Anurag, additional, Ritchie, Marylyn D., additional, and Klein, Teri E., additional
- Published
- 2019
- Full Text
- View/download PDF
11. Pharmacogenomics Clinical Annotation Tool (PharmCAT).
- Author
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Sangkuhl, Katrin, Whirl‐Carrillo, Michelle, Whaley, Ryan M., Woon, Mark, Lavertu, Adam, Altman, Russ B., Carter, Lester, Verma, Anurag, Ritchie, Marylyn D., and Klein, Teri E.
- Subjects
GENETIC testing ,INDIVIDUALIZED medicine ,ANNOTATIONS ,HAPLOTYPES ,MATERIALS testing ,REFERENCE sources ,PHARMACOGENOMICS - Abstract
Pharmacogenomics (PGx) decision support and return of results is an active area of precision medicine. One challenge of implementing PGx is extracting genomic variants and assigning haplotypes in order to apply prescribing recommendations and information from the Clinical Pharmacogenetics Implementation Consortium (CPIC), the US Food and Drug Administration (FDA), the Pharmacogenomics Knowledgebase (PharmGKB), etc. Pharmacogenomics Clinical Annotation Tool (PharmCAT) (i) extracts variants specified in guidelines from a genetic data set derived from sequencing or genotyping technologies, (ii) infers haplotypes and diplotypes, and (iii) generates a report containing genotype/diplotype‐based annotations and guideline recommendations. We describe PharmCAT and a pilot validation project comparing results for 1000 Genomes Project sequences of Coriell samples with corresponding Genetic Testing Reference Materials Coordination Program (GeT‐RM) sample characterization. PharmCAT was highly concordant with the GeT‐RM data. PharmCAT is available in GitHub to evaluate, test, and report results back to the community. As precision medicine becomes more prevalent, our ability to consistently, accurately, and clearly define and report PGx annotations and prescribing recommendations is critical. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
12. Integrating Large-Scale Genotype and Phenotype Data
- Author
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Hernandez-Boussard, Tina, primary, Woon, Mark, additional, Klein, Teri E., additional, and Altman, Russ B., additional
- Published
- 2006
- Full Text
- View/download PDF
13. Phased whole-genome genetic risk in a family quartet using a major allele reference sequence
- Author
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Michelle Whirl-Carrillo, Carlos Bustamante, Matthew T. Wheeler, Atul J. Butte, Emidio Capriotti, Katrin Sangkuhl, Kelly E. Ormond, Konrad J. Karczewski, Joshua W. Knowles, Joel T. Dudley, Russ B. Altman, Euan A. Ashley, Joan M. Hebert, Aleksandra Pavlovic, Mark Woon, Madeleine Ball, Teri E. Klein, Joseph V. Thakuria, Sergio Cordero, Anne West, John West, Jake K. Byrnes, Colleen Caleshu, George M. Church, Omar E. Cornejo, Heidi L. Rehm, Alexander Wait Zaranek, Frederick E. Dewey, Li Gong, Sean P. David, Michael Snyder, Rong Chen, Caroline F. Thorn, Dewey, Frederick E., Chen, Rong, Cordero, Sergio P., Ormond, Kelly E., Caleshu, Colleen, Karczewski, Konrad J., Whirl-Carrillo, Michelle, Wheeler, Matthew T., Dudley, Joel T., Byrnes, Jake K., Cornejo, Omar E., Knowles, Joshua W., Woon, Mark, Sangkuhl, Katrin, Gong, Li, Thorn, Caroline F., Hebert, Joan M., Capriotti, Emidio, David, Sean P., Pavlovic, Aleksandra, West, Anne, Thakuria, Joseph V., Ball, Madeleine P., Zaranek, Alexander W., Rehm, Heidi L., Church, George M., West, John S., Bustamante, Carlos D., Snyder, Michael, Altman, Russ B., Klein, Teri E., Butte, Atul J., Ashley, Euan A, and Copenhaver, Gregory P
- Subjects
Male ,Cancer Research ,DNA Mutational Analysis ,Genome-wide association study ,0302 clinical medicine ,Genes, Synthetic ,2.1 Biological and endogenous factors ,Thrombophilia ,Aetiology ,Genetics (clinical) ,Genetics ,0303 health sciences ,Genome ,Reference Standards ,3. Good health ,Pedigree ,030220 oncology & carcinogenesis ,Female ,Sequence Analysis ,Research Article ,Human ,Biotechnology ,lcsh:QH426-470 ,Genotype ,Biology ,Risk Assessment ,DNA sequencing ,03 medical and health sciences ,Genetic ,Genetic Mutation ,Genetic variation ,Humans ,Genetic Predisposition to Disease ,Allele ,Genotyping ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Alleles ,030304 developmental biology ,Base Sequence ,Genome, Human ,Haplotype ,Synthetic ,Human Genome ,Genetic Variation ,Human Genetics ,DNA ,Sequence Analysis, DNA ,Ecology, Evolution, Behavior and Systematic ,lcsh:Genetics ,Genes ,Haplotypes ,Genetics of Disease ,Human genome ,Generic health relevance ,Sequence Alignment ,Reference genome ,Developmental Biology ,Genome-Wide Association Study - Abstract
Whole-genome sequencing harbors unprecedented potential for characterization of individual and family genetic variation. Here, we develop a novel synthetic human reference sequence that is ethnically concordant and use it for the analysis of genomes from a nuclear family with history of familial thrombophilia. We demonstrate that the use of the major allele reference sequence results in improved genotype accuracy for disease-associated variant loci. We infer recombination sites to the lowest median resolution demonstrated to date (, Author Summary An individual's genetic profile plays an important role in determining risk for disease and response to medical therapy. The development of technologies that facilitate rapid whole-genome sequencing will provide unprecedented power in the estimation of disease risk. Here we develop methods to characterize genetic determinants of disease risk and response to medical therapy in a nuclear family of four, leveraging population genetic profiles from recent large scale sequencing projects. We identify the way in which genetic information flows through the family to identify sequencing errors and inheritance patterns of genes contributing to disease risk. In doing so we identify genetic risk factors associated with an inherited predisposition to blood clot formation and response to blood thinning medications. We find that this aligns precisely with the most significant disease to occur to date in the family, namely pulmonary embolism, a blood clot in the lung. These ethnicity-specific, family-based approaches to interpretation of individual genetic profiles are emblematic of the next generation of genetic risk assessment using whole-genome sequencing.
- Published
- 2011
14. PGxMine: Text mining for curation of PharmGKB.
- Author
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Lever J, Barbarino JM, Gong L, Huddart R, Sangkuhl K, Whaley R, Whirl-Carrillo M, Woon M, Klein TE, and Altman RB
- Subjects
- Computational Biology, Data Mining methods, Databases, Genetic, Humans, Knowledge Bases, Pharmacogenetics, Precision Medicine methods
- Abstract
Precision medicine tailors treatment to individuals personal data including differences in their genome. The Pharmacogenomics Knowledgebase (PharmGKB) provides highly curated information on the effect of genetic variation on drug response and side effects for a wide range of drugs. PharmGKB's scientific curators triage, review and annotate a large number of papers each year but the task is challenging. We present the PGxMine resource, a text-mined resource of pharmacogenomic associations from all accessible published literature to assist in the curation of PharmGKB. We developed a supervised machine learning pipeline to extract associations between a variant (DNA and protein changes, star alleles and dbSNP identifiers) and a chemical. PGxMine covers 452 chemicals and 2,426 variants and contains 19,930 mentions of pharmacogenomic associations across 7,170 papers. An evaluation by PharmGKB curators found that 57 of the top 100 associations not found in PharmGKB led to 83 curatable papers and a further 24 associations would likely lead to curatable papers through citations. The results can be viewed at https://pgxmine.pharmgkb.org/ and code can be downloaded at https://github.com/jakelever/pgxmine.
- Published
- 2020
15. Posterolateral dislocation of the knee: Recognizing an uncommon entity.
- Author
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Woon CY and Hutchinson MR
- Abstract
Posterolateral dislocations of the knee are rare injuries. Early recognition and emergent open reduction is crucial. A 48-year-old Caucasian male presented with right knee pain and limb swelling 3 d after sustaining a twisting injury in the bathroom. Examination revealed the pathognomonic anteromedial "pucker" sign. Ankle-brachial indices were greater than 1.0 and symmetrical. Radiographs showed a posterolateral dislocation of the right knee. He underwent emergency open reduction without an attempt at closed reduction. Attempts at closed reduction of posterolateral dislocations of the knee are usually impossible because of incarceration of medial soft tissue in the intercondylar notch and may only to delay surgical management and increase the risk of skin necrosis. Magnetic resonance imaging is not crucial in the preoperative period and can lead to delays of up to 24 h. Instead, open reduction should be performed once vascular compromise is excluded.
- Published
- 2016
- Full Text
- View/download PDF
16. Integrating large-scale genotype and phenotype data.
- Author
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Hernandez-Boussard T, Woon M, Klein TE, and Altman RB
- Subjects
- Animals, Genotype, Humans, Databases, Genetic statistics & numerical data, Phenotype
- Abstract
With the completion of the Human Genome Project, a new emphasis is focusing on the sequence variation and the resulting phenotype. The number of data available from genomic studies addressing this relationship is rapidly growing. In order to analyze these data as a whole, they need to be integrated, aggregated and annotated in a timely manner. The Pharmacogenetics and Pharmacogenomics Knowledge Base PharmGKB; (
) assembles and disseminates these data and their associated metadata that are needed for unambiguous identification and replication. Assembling these data in a timely manner is challenging, and the scalability of these data produce major challenges for a knowledge base such as PharmGKB. However, it is only through rapid global meta-annotation of these data that we will understand the relationship between specific genotype(s) and the related phenotype. PharmGKB has confronted these challenges, and these experiences and solutions can benefit all genome communities. - Published
- 2006
- Full Text
- View/download PDF
17. A resource to acquire and summarize pharmacogenetics knowledge in the literature.
- Author
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Rubin DL, Carrillo M, Woon M, Conroy J, Klein TE, and Altman RB
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- Genes, Internet, Pharmaceutical Preparations, Programming Languages, Databases, Bibliographic, Information Storage and Retrieval methods, Pharmacogenetics
- Abstract
To determine how genetic variations contribute the variations in drug response, we need to know the genes that are related to drugs of interest. But there are no publicly available data-bases of known gene-drug relationships, and it is time-consuming to search the literature for this information. We have developed a resource to support the storage, summarization, and dissemination of key gene-drug interactions of relevance to pharmacogenetics. Extracting all gene-drug relationships from the literature is a daunting task, so we distributed a tool to acquire this knowledge from the scientific community. We also developed a categorization scheme to classify gene-drug relationships according to the type of pharmacogenetic evidence that supports them. Our resource (http://www.pharmgkb.org/home/project-community.jsp) can be queried by gene or drug, and it summarizes gene-drug relationships, categories of evidence, and supporting literature. This resource is growing, containing entries for 138 genes and 215 drugs of pharmacogenetics significance, and is a core component of PharmGKB, a pharmacogenetics knowledge base (http://www.pharmgkb.org).
- Published
- 2004
18. A personalized and automated dbSNP surveillance system.
- Author
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Liu S, Lin S, Woon M, Klein TE, and Altman RB
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- Information Dissemination methods, Registries, Software, Systems Integration, DNA genetics, DNA Mutational Analysis methods, Database Management Systems, Databases, Genetic, Information Storage and Retrieval methods, Polymorphism, Single Nucleotide genetics, User-Computer Interface
- Abstract
The development of high throughput techniques and large-scale studies in the biological sciences has given rise to an explosive growth in both the volume and types of data available to researchers. A surveillance system that monitors data repositories and reports changes helps manage the data overload. We developed a dbSNP surveillance system (URL: http://www.pharmgkb.org/do/serve?id=tools.surveillance.dbsnp) that performs surveillance on the dbSNP database and alerts users to new information. The system is notable because it is personalized and fully automated. Each registered user has a list of genes to follow and receives notification of new entries concerning these genes. The system integrates data from dbSNP, LocusLink, PharmGKB, and Genbank to position SNPs on reference sequences and classify SNPs into categories such as synonymous and non-synonymous SNPs. The system uses data warehousing, object model-based data integration, object-oriented programming, and a platform-neutral data access mechanism.
- Published
- 2003
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