The Experts below are selected from a list of 240 Experts worldwide ranked by ideXlab platform
S D M Brown - One of the best experts on this subject based on the ideXlab platform.
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lama automated image analysis for developmental Phenotyping of Mouse embryos
bioRxiv, 2020Co-Authors: Neil R Horner, S D M Brown, Shanmugasundaram Venkataraman, Ramon Casero, James M Brown, Sara J Johnson, Lydia Teboul, Sara Wells, Henrik Westerberg, Annmarie MallonAbstract:Advanced 3D imaging modalities such as micro computed tomography (micro-CT), high resolution episcopic microscopy (HREM), and optical projection tomography (OPT) have been readily incorporated into high-throughput Phenotyping pipelines, such as the International Mouse Phenotyping Consortium (IMPC). Such modalities generate large volumes of raw data that cannot be immediately harnessed without significant resources of manpower and expertise. Thus, rapid automated analysis and annotation is critical to ensure that 3D imaging data is able to be integrated with other multi-dimensional Phenotyping data. To this end, we present an automated computational Mouse Phenotyping pipeline called LAMA, based on image registration, which requires minimal technical expertise and human input to use. Designed predominantly for developmental biologists, our software performs image pre-processing, registration, statistical and gene function annotation, and segmentation of 3D micro-CT data. We address several limitations of current methods and create an easy to use, fast solution application for Mouse embryo Phenotyping. We also present a highly granular, novel anatomical E14.5 (14.5 days post coitus) atlas of a population average that integrates with our pipeline to allow a range of dysmorphologies to be automatically annotated as well as results from the validation of the pipeline.
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The dark genome and pleiotropy: challenges for precision medicine
Mammalian Genome, 2019Co-Authors: S D M BrownAbstract:Surprisingly we remain ignorant of the function of the majority of genes in the human and Mouse genomes. The dark genome is a major obstacle to the interpretation of the function of human genetic variation and its impact on disease. At the same time, pleiotropy, how individual variants influence multiple phenotypes, is key to understanding gene function and the role of genes and genetic networks in disease systems. Both understanding the genetics of disease and developing new therapeutic approaches and advances in precision medicine are all compromised by our limited knowledge of gene function and pleiotropic effects. Illuminating the dark genome and revealing pleiotropy across the genome requires a highly coordinated and international effort to acquire and analyse high-dimensional phenotype data from model organisms. We describe briefly how the International Mouse Phenotyping Consortium is addressing these challenges and the novel features of the pleiotropic landscape that are revealed by functional genomics programmes at genome-wide scale.
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the international Mouse Phenotyping consortium impc a functional catalogue of the mammalian genome that informs conservation
Conservation Genetics, 2018Co-Authors: Violeta Munozfuentes, S D M Brown, Terrence F Meehan, Paul Flicek, Pilar Cacheiro, Juan Antonio Aguilarpimentel, Ann M Flenniken, Antonella Galli, Hamed Haseli Mashhadi, Martin Hrabě De AngelisAbstract:The International Mouse Phenotyping Consortium (IMPC) is building a catalogue of mammalian gene function by producing and Phenotyping a knockout Mouse line for every protein-coding gene. To date, the IMPC has generated and characterised 5186 mutant lines. One-third of the lines have been found to be non-viable and over 300 new Mouse models of human disease have been identified thus far. While current bioinformatics efforts are focused on translating results to better understand human disease processes, IMPC data also aids understanding genetic function and processes in other species. Here we show, using gorilla genomic data, how genes essential to development in mice can be used to help assess the potentially deleterious impact of gene variants in other species. This type of analyses could be used to select optimal breeders in endangered species to maintain or increase fitness and avoid variants associated to impaired-health phenotypes or loss-of-function mutations in genes of critical importance. We also show, using selected examples from various mammal species, how IMPC data can aid in the identification of candidate genes for studying a condition of interest, deliver information about the mechanisms involved, or support predictions for the function of genes that may play a role in adaptation. With genotyping costs decreasing and the continued improvements of bioinformatics tools, the analyses we demonstrate can be routinely applied.
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Accessing data from the International Mouse Phenotyping Consortium: state of the art and future plans
Mammalian Genome, 2012Co-Authors: Annmarie Mallon, S D M Brown, Hugh Morgan, Vivek Iyer, David Melvin, Helen Parkinson, Paul Flicek, William C. SkarnesAbstract:The International Mouse Phenotyping Consortium (IMPC) ( http://www.Mousephenotype.org ) will reveal the pleiotropic functions of every gene in the Mouse genome and uncover the wider role of genetic loci within diverse biological systems. Comprehensive informatics solutions are vital to ensuring that this vast array of data is captured in a standardised manner and made accessible to the scientific community for interrogation and analysis. Here we review the existing EuroPhenome and WTSI phenotype informatics systems and the IKMC portal, and present plans for extending these systems and lessons learned to the development of a robust IMPC informatics infrastructure.
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the international Mouse Phenotyping consortium past and future perspectives on Mouse Phenotyping
Mammalian Genome, 2012Co-Authors: S D M Brown, Mark W MooreAbstract:Determining the function of all mammalian genes remains a major challenge for the biomedical science community in the 21st century. The goal of the International Mouse Phenotyping Consortium (IMPC) over the next 10 years is to undertake broad-based Phenotyping of 20,000 Mouse genes, providing an unprecedented insight into mammalian gene function. This short article explores the drivers for large-scale Mouse Phenotyping and provides an overview of the aims and processes involved in IMPC Mouse production and Phenotyping.
Terrence F Meehan - One of the best experts on this subject based on the ideXlab platform.
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The International Mouse Phenotyping Consortium (IMPC): a functional catalogue of the mammalian genome that informs conservation · the IMPC consortium
2020Co-Authors: Violeta Muñoz-fuentes, Terrence F Meehan, Paul Flicek, Pilar Cacheiro, Ann M Flenniken, Antonella Galli, Hamed Haseli Mashhadi, Steve Brown, Juan Antonio Aguilar-pimentel, Martin Hrabě De AngelisAbstract:The International Mouse Phenotyping Consortium (IMPC) is building a catalogue of mammalian gene function by producing and Phenotyping a knockout Mouse line for every protein-coding gene. To date, the IMPC has generated and characterised 5186 mutant lines. One-third of the lines have been found to be non-viable and over 300 new Mouse models of human disease have been identified thus far. While current bioinformatics efforts are focused on translating results to better understand human disease processes, IMPC data also aids understanding genetic function and processes in other species. Here we show, using gorilla genomic data, how genes essential to development in mice can be used to help assess the potentially deleterious impact of gene variants in other species. This type of analyses could be used to select optimal breeders in endangered species to maintain or increase fitness and avoid variants associated to impaired-health phenotypes or loss-of-function mutations in genes of critical importance. We also show, using selected examples from various mammal species, how IMPC data can aid in the identification of candidate genes for studying a condition of interest, deliver information about the mechanisms involved, or support predictions for the function of genes that may play a role in adaptation. With genotyping costs decreasing and the continued improvements of bioinformatics tools, the analyses we demonstrate can be routinely applied.
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the international Mouse Phenotyping consortium impc a functional catalogue of the mammalian genome that informs conservation
Conservation Genetics, 2018Co-Authors: Violeta Munozfuentes, S D M Brown, Terrence F Meehan, Paul Flicek, Pilar Cacheiro, Juan Antonio Aguilarpimentel, Ann M Flenniken, Antonella Galli, Hamed Haseli Mashhadi, Martin Hrabě De AngelisAbstract:The International Mouse Phenotyping Consortium (IMPC) is building a catalogue of mammalian gene function by producing and Phenotyping a knockout Mouse line for every protein-coding gene. To date, the IMPC has generated and characterised 5186 mutant lines. One-third of the lines have been found to be non-viable and over 300 new Mouse models of human disease have been identified thus far. While current bioinformatics efforts are focused on translating results to better understand human disease processes, IMPC data also aids understanding genetic function and processes in other species. Here we show, using gorilla genomic data, how genes essential to development in mice can be used to help assess the potentially deleterious impact of gene variants in other species. This type of analyses could be used to select optimal breeders in endangered species to maintain or increase fitness and avoid variants associated to impaired-health phenotypes or loss-of-function mutations in genes of critical importance. We also show, using selected examples from various mammal species, how IMPC data can aid in the identification of candidate genes for studying a condition of interest, deliver information about the mechanisms involved, or support predictions for the function of genes that may play a role in adaptation. With genotyping costs decreasing and the continued improvements of bioinformatics tools, the analyses we demonstrate can be routinely applied.
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the international Mouse Phenotyping consortium impc a functional catalogue of the mammalian genome that informs conservation the impc consortium
2018Co-Authors: Violeta Munozfuentes, Terrence F Meehan, Paul Flicek, Pilar Cacheiro, Juan Antonio Aguilarpimentel, Ann M Flenniken, Antonella Galli, Hamed Haseli Mashhadi, Steve Brown, Martin Hrabě De AngelisAbstract:The International Mouse Phenotyping Consortium (IMPC) is building a catalogue of mammalian gene function by producing and Phenotyping a knockout Mouse line for every protein-coding gene. To date, the IMPC has generated and characterised 5186 mutant lines. One-third of the lines have been found to be non-viable and over 300 new Mouse models of human disease have been identified thus far. While current bioinformatics efforts are focused on translating results to better understand human disease processes, IMPC data also aids understanding genetic function and processes in other species. Here we show, using gorilla genomic data, how genes essential to development in mice can be used to help assess the potentially deleterious impact of gene variants in other species. This type of analyses could be used to select optimal breeders in endangered species to maintain or increase fitness and avoid variants associated to impaired-health phenotypes or loss-of-function mutations in genes of critical importance. We also show, using selected examples from various mammal species, how IMPC data can aid in the identification of candidate genes for studying a condition of interest, deliver information about the mechanisms involved, or support predictions for the function of genes that may play a role in adaptation. With genotyping costs decreasing and the continued improvements of bioinformatics tools, the analyses we demonstrate can be routinely applied.
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disease model discovery from 3 328 gene knockouts by the international Mouse Phenotyping consortium
Nature Genetics, 2017Co-Authors: Terrence F Meehan, Nathalie Conte, David B West, Julius O B Jacobsen, Jeremy Mason, Jonathan Warren, Chao Kung Chen, Ilinca Tudose, Mike Relac, Peter MatthewsAbstract:Damian Smedley and colleagues report the phenotypic characterization of the first 3,328 genes by the International Mouse Phenotyping Consortium. They develop new Mouse models based on genes known to be associated with human mendelian diseases and identify potential disease-associated genes with little or no previous functional annotation.
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Reporting phenotypes in Mouse models when considering body size as a potential confounder
Journal of Biomedical Semantics, 2016Co-Authors: Anika Oellrich, Terrence F Meehan, Helen Parkinson, Sirarat Sarntivijai, Jacqueline K. White, Natasha A KarpAbstract:Genotype-phenotype studies aim to identify causative relationships between genes and phenotypes. The International Mouse Phenotyping Consortium is a high throughput Phenotyping program whose goal is to collect phenotype data for a knockout Mouse strain of every protein coding gene. The scale of the project requires an automatic analysis pipeline to detect abnormal phenotypes, and disseminate the resulting gene-phenotype annotation data into public resources. A body weight phenotype is a common result of knockout studies. As body weight correlates with many other biological traits, this challenges the interpretation of related gene-phenotype associations. Co-correlation can lead to gene-phenotype associations that are potentially misleading. Here we use statistical modelling to account for body weight as a potential confounder to assess the impact. We find that there is a considerable impact on previously established gene-phenotype associations due to an increase in sensitivity as well as the confounding effect. We investigated the existing ontologies to represent this phenotypic information and we explored ways to ontologically represent the results of the influence of confounders on gene-phenotype associations. With the scale of data being disseminated within the high throughput programs and the range of downstream studies that utilise these data, it is critical to consider how we improve the quality of the disseminated data and provide a robust ontological representation.
Annmarie Mallon - One of the best experts on this subject based on the ideXlab platform.
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lama automated image analysis for developmental Phenotyping of Mouse embryos
bioRxiv, 2020Co-Authors: Neil R Horner, S D M Brown, Shanmugasundaram Venkataraman, Ramon Casero, James M Brown, Sara J Johnson, Lydia Teboul, Sara Wells, Henrik Westerberg, Annmarie MallonAbstract:Advanced 3D imaging modalities such as micro computed tomography (micro-CT), high resolution episcopic microscopy (HREM), and optical projection tomography (OPT) have been readily incorporated into high-throughput Phenotyping pipelines, such as the International Mouse Phenotyping Consortium (IMPC). Such modalities generate large volumes of raw data that cannot be immediately harnessed without significant resources of manpower and expertise. Thus, rapid automated analysis and annotation is critical to ensure that 3D imaging data is able to be integrated with other multi-dimensional Phenotyping data. To this end, we present an automated computational Mouse Phenotyping pipeline called LAMA, based on image registration, which requires minimal technical expertise and human input to use. Designed predominantly for developmental biologists, our software performs image pre-processing, registration, statistical and gene function annotation, and segmentation of 3D micro-CT data. We address several limitations of current methods and create an easy to use, fast solution application for Mouse embryo Phenotyping. We also present a highly granular, novel anatomical E14.5 (14.5 days post coitus) atlas of a population average that integrates with our pipeline to allow a range of dysmorphologies to be automatically annotated as well as results from the validation of the pipeline.
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Correction of the auditory phenotype in C57BL/6N mice via CRISPR/Cas9-mediated homology directed repair
Genome Medicine, 2016Co-Authors: Joffrey Mianné, Annmarie Mallon, Sara Wells, Lauren Chessum, Saumya Kumar, Carlos Aguilar, Gemma Codner, Marie Hutchison, Andrew Parker, Michelle M. SimonAbstract:Background Nuclease-based technologies have been developed that enable targeting of specific DNA sequences directly in the zygote. These approaches provide an opportunity to modify the genomes of inbred mice, and allow the removal of strain-specific mutations that confound phenotypic assessment. One such mutation is the Cdh23 ^ ahl allele, present in several commonly used inbred Mouse strains, which predisposes to age-related progressive hearing loss. Results We have used targeted CRISPR/Cas9-mediated homology directed repair (HDR) to correct the Cdh23 ^ ahl allele directly in C57BL/6NTac zygotes. Employing offset-nicking Cas9 (D10A) nickase with paired RNA guides and a single-stranded oligonucleotide donor template we show that allele repair was successfully achieved. To investigate potential Cas9-mediated ‘off-target’ mutations in our corrected Mouse, we undertook whole-genome sequencing and assessed the ‘off-target’ sites predicted for the guide RNAs (≤4 nucleotide mis-matches). No induced sequence changes were identified at any of these sites. Correction of the progressive hearing loss phenotype was demonstrated using auditory-evoked brainstem response testing of mice at 24 and 36 weeks of age, and rescue of the progressive loss of sensory hair cell stereocilia bundles was confirmed using scanning electron microscopy of dissected cochleae from 36-week-old mice. Conclusions CRISPR/Cas9-mediated HDR has been successfully utilised to efficiently correct the Cdh23 ^ ahl allele in C57BL/6NTac mice, and rescue the associated auditory phenotype. The corrected mice described in this report will allow age-related auditory Phenotyping studies to be undertaken using C57BL/6NTac-derived models, such as those generated by the International Mouse Phenotyping Consortium (IMPC) programme.
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Accessing and mining data from large-scale Mouse Phenotyping projects.
International Review of Neurobiology, 2012Co-Authors: Hugh Morgan, Michelle Simon, Annmarie MallonAbstract:Abstract Comprehensive Phenotyping through the International Mouse Phenotyping Consortium (IMPC)— www.Mousephenotype.org —will reveal the pleiotropic functions of every gene in the Mouse genome and uncover the wider role of genetic loci within diverse biological systems. The informatics challenge will be to develop an infrastructure to acquire the diverse and complex data sets generated from broad-based Phenotyping and disseminate these data in an integrated manner to the scientific community. We describe here the current methodologies implemented to capture and disseminate these data, and plans within the Knockout Mouse Phenotyping Project (KOMP2) ( http://commonfund.nih.gov/KOMP2/ )-funded informatics consortium to scale these implementations to manage the surge in data from the IMPC.
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Accessing data from the International Mouse Phenotyping Consortium: state of the art and future plans
Mammalian Genome, 2012Co-Authors: Annmarie Mallon, S D M Brown, Hugh Morgan, Vivek Iyer, David Melvin, Helen Parkinson, Paul Flicek, William C. SkarnesAbstract:The International Mouse Phenotyping Consortium (IMPC) ( http://www.Mousephenotype.org ) will reveal the pleiotropic functions of every gene in the Mouse genome and uncover the wider role of genetic loci within diverse biological systems. Comprehensive informatics solutions are vital to ensuring that this vast array of data is captured in a standardised manner and made accessible to the scientific community for interrogation and analysis. Here we review the existing EuroPhenome and WTSI phenotype informatics systems and the IKMC portal, and present plans for extending these systems and lessons learned to the development of a robust IMPC informatics infrastructure.
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high throughput Mouse Phenotyping
Methods, 2011Co-Authors: Hilary Gates, Annmarie Mallon, S D M BrownAbstract:Comprehensive Phenotyping will be required to reveal the pleiotropic functions of a gene and to uncover the wider role of genetic loci within diverse biological systems. The challenge will be to devise Phenotyping approaches to characterise the thousands of mutants that are being generated as part of international efforts to acquire a mutant for every gene in the Mouse genome. In order to acquire robust datasets of broad based phenotypes from Mouse mutants it is necessary to design and implement pipelines that incorporate standardised Phenotyping platforms that are validated across diverse Mouse genetics centres or Mouse clinics. We describe here the rationale and methodology behind one Phenotyping pipeline, EMPReSSslim, that was designed as part of the work of the EUMORPHIA and EUMODIC consortia, and which exemplifies some of the challenges facing large-scale Phenotyping. EMPReSSslim captures a broad range of data on diverse biological systems, from biochemical to physiological amongst others. Data capture and dissemination is pivotal to the operation of large-scale Phenotyping pipelines, including the definition of parameters integral to each Phenotyping test and the associated ontological descriptions. EMPReSSslim data is displayed within the EuroPhenome database, where a variety of tools are available to allow the user to search for interesting biological or clinical phenotypes.
Andrew Blake - One of the best experts on this subject based on the ideXlab platform.
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A Mouse informatics platform for phenotypic and translational discovery
Mammalian Genome, 2015Co-Authors: Natalie Ring, Andrew Blake, Terrence F Meehan, Nathalie Conte, Chao Kung Chen, Armida Di Fenza, James Brown, Tanja Fiegel, Neil Horner, Julius O B JacobsenAbstract:The International Mouse Phenotyping Consortium (IMPC) is providing the world’s first functional catalogue of a mammalian genome by characterising a knockout Mouse strain for every gene. A robust and highly structured informatics platform has been developed to systematically collate, analyse and disseminate the data produced by the IMPC. As the first phase of the project, in which 5000 new knockout strains are being broadly phenotyped, nears completion, the informatics platform is extending and adapting to support the increasing volume and complexity of the data produced as well as addressing a large volume of users and emerging user groups. An intuitive interface helps researchers explore IMPC data by giving overviews and the ability to find and visualise data that support a phenotype assertion. Dedicated disease pages allow researchers to find new Mouse models of human diseases, and novel viewers provide high-resolution images of embryonic and adult dysmorphologies. With each monthly release, the informatics platform will continue to evolve to support the increased data volume and to maintain its position as the primary route of access to IMPC data and as an invaluable resource for clinical and non-clinical researchers.
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the international Mouse Phenotyping consortium web portal a unified point of access for knockout mice and related Phenotyping data
Nucleic Acids Research, 2014Co-Authors: Gautier Koscielny, Andrew Blake, Hugh Morgan, Terrence F Meehan, Chao Kung Chen, Vivek Iyer, Gagarine Yaikhom, Julian Atienzaherrero, Richard Easty, Armida Di FenzaAbstract:The International Mouse Phenotyping Consortium (IMPC) web portal (http://www.Mousephenotype.org) provides the biomedical community with a unified point of access to mutant mice and rich collection of related emerging and existing Mouse phenotype data. IMPC Mouse clinics worldwide follow rigorous highly structured and standardized protocols for the experimentation, collection and dissemination of data. Dedicated 'data wranglers' work with each Phenotyping center to collate data and perform quality control of data. An automated statistical analysis pipeline has been developed to identify knockout strains with a significant change in the phenotype parameters. Annotation with biomedical ontologies allows biologists and clinicians to easily find Mouse strains with phenotypic traits relevant to their research. Data integration with other resources will provide insights into mammalian gene function and human disease. As phenotype data become available for every gene in the Mouse, the IMPC web portal will become an invaluable tool for researchers studying the genetic contributions of genes to human diseases.
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europhenome a repository for high throughput Mouse Phenotyping data
Nucleic Acids Research, 2010Co-Authors: Hugh Morgan, Andrew Blake, Holger Maier, Christoph Lengger, Hilary Gates, Tim Beck, Niels C Adams, Guillaume Debouzy, Sophie Leblanc, David MelvinAbstract:The broad aim of biomedical science in the postgenomic era is to link genomic and phenotype information to allow deeper understanding of the processes leading from genomic changes to altered phenotype and disease. The EuroPhenome project (http://www.EuroPhenome.org) is a comprehensive resource for raw and annotated high-throughput Phenotyping data arising from projects such as EUMODIC. EUMODIC is gathering data from the EMPReSSslim pipeline (http://www.empress.har.mrc.ac.uk/) which is performed on inbred Mouse strains and knock-out lines arising from the EUCOMM project. The EuroPhenome interface allows the user to access the data via the phenotype or genotype. It also allows the user to access the data in a variety of ways, including graphical display, statistical analysis and access to the raw data via web services. The raw Phenotyping data captured in EuroPhenome is annotated by an annotation pipeline which automatically identifies statistically different mutants from the appropriate baseline and assigns ontology terms for that specific test. Mutant phenotypes can be quickly identified using two EuroPhenome tools: PhenoMap, a graphical representation of statistically relevant phenotypes, and mining for a mutant using ontology terms. To assist with data definition and cross-database comparisons, phenotype data is annotated using combinations of terms from biological ontologies.
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europhenome and empress online Mouse Phenotyping resource
Nucleic Acids Research, 2007Co-Authors: Annmarie Mallon, Andrew Blake, John M HancockAbstract:EuroPhenome (http://www.europhenome.org) and EMPReSS (http://empress.har.mrc.ac.uk/) form an integrated resource to provide access to data and procedures for Mouse Phenotyping. EMPReSS describes 96 Standard Operating Procedures for Mouse Phenotyping. EuroPhenome contains data resulting from carrying out EMPReSS protocols on four inbred laboratory Mouse strains. As well as web interfaces, both resources support web services to enable integration with other Mouse Phenotyping and functional genetics resources, and are committed to initiatives to improve integration of Mouse phenotype databases. EuroPhenome will be the repository for a recently initiated effort to carry out large-scale Phenotyping on a large number of knockout Mouse lines (EUMODIC).
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empress european Mouse Phenotyping resource for standardized screens
Bioinformatics, 2005Co-Authors: Eain C J Green, Andrew Blake, Georgios V Gkoutos, Joseph Weekes, John M HancockAbstract:Summary: Standardized Phenotyping protocols are essential for the characterization of phenotypes so that results are comparable between different laboratories and phenotypic data can be related to ontological descriptions in an automated manner. We describe a web-based resource for the visualization, searching and downloading of standard operating procedures and other documents, the European Mouse Phenotyping Resource for Standardized Screens---EMPReSS. Availability: Direct access: http://www.empress.har.mrc.ac.uk Contact: e.green@har.mrc.ac.uk
Hugh Morgan - One of the best experts on this subject based on the ideXlab platform.
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the international Mouse Phenotyping consortium web portal a unified point of access for knockout mice and related Phenotyping data
Nucleic Acids Research, 2014Co-Authors: Gautier Koscielny, Andrew Blake, Hugh Morgan, Terrence F Meehan, Chao Kung Chen, Vivek Iyer, Gagarine Yaikhom, Julian Atienzaherrero, Richard Easty, Armida Di FenzaAbstract:The International Mouse Phenotyping Consortium (IMPC) web portal (http://www.Mousephenotype.org) provides the biomedical community with a unified point of access to mutant mice and rich collection of related emerging and existing Mouse phenotype data. IMPC Mouse clinics worldwide follow rigorous highly structured and standardized protocols for the experimentation, collection and dissemination of data. Dedicated 'data wranglers' work with each Phenotyping center to collate data and perform quality control of data. An automated statistical analysis pipeline has been developed to identify knockout strains with a significant change in the phenotype parameters. Annotation with biomedical ontologies allows biologists and clinicians to easily find Mouse strains with phenotypic traits relevant to their research. Data integration with other resources will provide insights into mammalian gene function and human disease. As phenotype data become available for every gene in the Mouse, the IMPC web portal will become an invaluable tool for researchers studying the genetic contributions of genes to human diseases.
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Accessing and mining data from large-scale Mouse Phenotyping projects.
International Review of Neurobiology, 2012Co-Authors: Hugh Morgan, Michelle Simon, Annmarie MallonAbstract:Abstract Comprehensive Phenotyping through the International Mouse Phenotyping Consortium (IMPC)— www.Mousephenotype.org —will reveal the pleiotropic functions of every gene in the Mouse genome and uncover the wider role of genetic loci within diverse biological systems. The informatics challenge will be to develop an infrastructure to acquire the diverse and complex data sets generated from broad-based Phenotyping and disseminate these data in an integrated manner to the scientific community. We describe here the current methodologies implemented to capture and disseminate these data, and plans within the Knockout Mouse Phenotyping Project (KOMP2) ( http://commonfund.nih.gov/KOMP2/ )-funded informatics consortium to scale these implementations to manage the surge in data from the IMPC.
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Accessing data from the International Mouse Phenotyping Consortium: state of the art and future plans
Mammalian Genome, 2012Co-Authors: Annmarie Mallon, S D M Brown, Hugh Morgan, Vivek Iyer, David Melvin, Helen Parkinson, Paul Flicek, William C. SkarnesAbstract:The International Mouse Phenotyping Consortium (IMPC) ( http://www.Mousephenotype.org ) will reveal the pleiotropic functions of every gene in the Mouse genome and uncover the wider role of genetic loci within diverse biological systems. Comprehensive informatics solutions are vital to ensuring that this vast array of data is captured in a standardised manner and made accessible to the scientific community for interrogation and analysis. Here we review the existing EuroPhenome and WTSI phenotype informatics systems and the IKMC portal, and present plans for extending these systems and lessons learned to the development of a robust IMPC informatics infrastructure.
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europhenome a repository for high throughput Mouse Phenotyping data
Nucleic Acids Research, 2010Co-Authors: Hugh Morgan, Andrew Blake, Holger Maier, Christoph Lengger, Hilary Gates, Tim Beck, Niels C Adams, Guillaume Debouzy, Sophie Leblanc, David MelvinAbstract:The broad aim of biomedical science in the postgenomic era is to link genomic and phenotype information to allow deeper understanding of the processes leading from genomic changes to altered phenotype and disease. The EuroPhenome project (http://www.EuroPhenome.org) is a comprehensive resource for raw and annotated high-throughput Phenotyping data arising from projects such as EUMODIC. EUMODIC is gathering data from the EMPReSSslim pipeline (http://www.empress.har.mrc.ac.uk/) which is performed on inbred Mouse strains and knock-out lines arising from the EUCOMM project. The EuroPhenome interface allows the user to access the data via the phenotype or genotype. It also allows the user to access the data in a variety of ways, including graphical display, statistical analysis and access to the raw data via web services. The raw Phenotyping data captured in EuroPhenome is annotated by an annotation pipeline which automatically identifies statistically different mutants from the appropriate baseline and assigns ontology terms for that specific test. Mutant phenotypes can be quickly identified using two EuroPhenome tools: PhenoMap, a graphical representation of statistically relevant phenotypes, and mining for a mutant using ontology terms. To assist with data definition and cross-database comparisons, phenotype data is annotated using combinations of terms from biological ontologies.