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419 results on '"Mallon, Ann-Marie"'

102. AnN-Ethyl-N-Nitrosourea (ENU) Mutagenized Mouse Model for Autosomal Dominant Nonsyndromic Kyphoscoliosis Due to Vertebral Fusion

Author

Esapa, Christopher T, primary, Piret, Sian E, additional, Nesbit, M Andrew, additional, Thomas, Gethin P, additional, Coulton, Leslie A, additional, Gallagher, Orla M, additional, Simon, Michelle M, additional, Kumar, Saumya, additional, Mallon, Ann-Marie, additional, Bellantuono, Ilaria, additional, Brown, Matthew A, additional, Croucher, Peter I, additional, Potter, Paul K, additional, Brown, Steve DM, additional, Cox, Roger D, additional, and Thakker, Rajesh V, additional

Published
2018
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103. A mutation in Nischarin causes otitis media via LIMK1 and NF-κB pathways

Author

Justice, Monica J., Crompton, Michael, Purnell, Tom, Tyrer, Hayley, Parker, Andrew, Ball, Greg, Hardisty-Hughes, Rachel E., Gale, Richard, Williams, Debbie, Dean, Charlotte H., Simon, Michelle M., Mallon, Ann-Marie, Wells, Sara, Bhutta, Mahmood F., Burton, Martin J., Tateossian, Hilda, Brown, Steve D. M., Justice, Monica J., Crompton, Michael, Purnell, Tom, Tyrer, Hayley, Parker, Andrew, Ball, Greg, Hardisty-Hughes, Rachel E., Gale, Richard, Williams, Debbie, Dean, Charlotte H., Simon, Michelle M., Mallon, Ann-Marie, Wells, Sara, Bhutta, Mahmood F., Burton, Martin J., Tateossian, Hilda, and Brown, Steve D. M.

Abstract

Otitis media (OM), inflammation of the middle ear (ME), is a common cause of conductive hearing impairment. Despite the importance of the disease, the aetiology of chronic and recurrent forms of middle ear inflammatory disease remains poorly understood. Studies of the human population suggest that there is a significant genetic component predisposing to the development of chronic OM, although the underlying genes are largely unknown. Using N-ethyl-N-nitrosourea mutagenesis we identified a recessive mouse mutant, edison, that spontaneously develops a conductive hearing loss due to chronic OM. The causal mutation was identified as a missense change, L972P, in the Nischarin (NISCH) gene. edison mice develop a serous or granulocytic effusion, increasingly macrophage and neutrophil rich with age, along with a thickened, inflamed mucoperiosteum. We also identified a second hypomorphic allele, V33A, with only modest increases in auditory thresholds and reduced incidence of OM. NISCH interacts with several proteins, including ITGA5 that is thought to have a role in modulating VEGF-induced angiogenesis and vascularization. We identified a significant genetic interaction between Nisch and Itga5; mice heterozygous for Itga5-null and homozygous for edison mutations display a significantly increased penetrance and severity of chronic OM. In order to understand the pathological mechanisms underlying the OM phenotype, we studied interacting partners to NISCH along with downstream signalling molecules in the middle ear epithelia of edison mouse. Our analysis implicates PAK1 and RAC1, and downstream signalling in LIMK1 and NF-κB pathways in the development of chronic OM.

Published
2017

105. A mutation in Nischarin causes otitis media via LIMK1 and NF-κB pathways

Author

Crompton, Michael, primary, Purnell, Tom, additional, Tyrer, Hayley E., additional, Parker, Andrew, additional, Ball, Greg, additional, Hardisty-Hughes, Rachel E., additional, Gale, Richard, additional, Williams, Debbie, additional, Dean, Charlotte H., additional, Simon, Michelle M., additional, Mallon, Ann-Marie, additional, Wells, Sara, additional, Bhutta, Mahmood F., additional, Burton, Martin J., additional, Tateossian, Hilda, additional, and Brown, Steve D. M., additional

Published
2017
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106. The Early Detection of Neurodegenerative diseases initiative: an international and multidisciplinary effort for transforming the early detection of dementia‐causing diseases.

Author

Marinaro, Federica, Morvan, Claire, Au, Rhoda, Bond, Simon, Burkhart, Michael C., Carlebach, Nomi, Chan, Dennis, Delbarre, Daniel, Farier, Lisa, Lacey, Aaron, LaMonica, Haley, Lancaster, Claire L, Lee, Liz Yuanxi, Llewellyn, David J, Mallon, Ann‐Marie, Martins, Ralph N, Ardle, Ríona Mc, Mummery, Catherine J., Naismith, Sharon L, and Oldham, Mike

Abstract

Background: Around 50 million people have dementia worldwide, with nearly 10 million new cases every year. Diagnosis is complex and often relies on expensive and invasive measures, with most patients accessing medical support when they already experience symptoms. Method: The Early Detection of Neurodegenerative diseases (EDoN) initiative, spearheaded by Alzheimer's Research UK, brings together over 60 experts from 49 universities, research projects, patient cohorts and technology providers to create machine learning models to detect the earliest stages of dementia‐causing diseases. EDoN has reviewed behavioural and physiological modalities with the strongest association with pre‐clinical disease. Result: Over 140 modalities were identified from the review and were shortlisted to create the version 1 digital toolkit. This first version includes Mezurio and Longevity smartphone apps, a Fitbit charge 4 activity tracker and Dreem 3 sleep headband. This Toolkit was further refined through patient and public involvement studies and collects 26 measures related to 7 aspects of behaviour and physiology (cognition, neural activity, physical activity, heart rate, fine motor movement, sleep, language and speech). The Toolkit is now being used to collect digital data in four international cohorts (Boston University Alzheimer's Disease Research Center ‐ BU ADRC; The predictors of COgnitive DECline in attenders of memory clinic using digital devices ‐ CODEC‐2; Western Australia Memory Study ‐ WAMS; Healthy Brain Aging ‐ HBA), alongside prospective and retrospective clinical data, to inform the development of machine learning models. Conclusion: EDoN will build models with digital markers, validating them against other biomarkers to predict dementia subtypes and individualised disease trajectories. Based on the outputs of the initial models, EDoN will go through a series of iterations of cohort engagement, modality and tool refinement, and data collection. Workstreams are underway to inform data security, privacy, ethics and open policy research, as well as considering the integration of the final EDoN Toolkit into healthcare systems globally. EDoN aims to deliver a cost‐effective, low burden and population‐wide method for early detection of dementia‐causing diseases that will benefit the public, patients, carers, researchers and clinicians, as well as the broader healthcare system and the delivery of new therapies. [ABSTRACT FROM AUTHOR]

Published
2023
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107. Genetic background influences tumour development in heterozygous Men1knockout mice

Author

Lines, Kate E, Javid, Mahsa, Reed, Anita A C, Walls, Gerard V, Stevenson, Mark, Simon, Michelle, Kooblall, Kreepa G, Piret, Sian E, Christie, Paul T, Newey, Paul J, Mallon, Ann-Marie, and Thakker, Rajesh V

Abstract

Multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder caused by MEN1germline mutations, is characterised by parathyroid, pancreatic and pituitary tumours. MEN1mutations also cause familial isolated primary hyperparathyroidism (FIHP), a milder condition causing hyperparathyroidism only. Identical mutations can cause either MEN1 or FIHP in different families, thereby implicating a role for genetic modifiers in altering phenotypic expression of tumours. We therefore investigated the effects of genetic background and potential for genetic modifiers on tumour development in adult Men1+/-mice, which develop tumours of the parathyroids, pancreatic islets, anterior pituitary, adrenal cortex and gonads, that had been backcrossed to generate C57BL/6 and 129S6/SvEv congenic strains. A total of 275 Men1+/-mice, aged 5–26 months were macroscopically studied, and this revealed that genetic background significantly influenced the development of pituitary, adrenal and ovarian tumours, which occurred in mice over 12 months of age and more frequently in C57BL/6 females, 129S6/SvEv males and 129S6/SvEv females, respectively. Moreover, pituitary and adrenal tumours developed earlier, in C57BL/6 males and 129S6/SvEv females, respectively, and pancreatic and testicular tumours developed earlier in 129S6/SvEv males. Furthermore, glucagon-positive staining pancreatic tumours occurred more frequently in 129S6/SvEv Men1+/-mice. Whole genome sequence analysis of 129S6/SvEv and C57BL/6 Men1+/-mice revealed >54,000 different variants in >300 genes. These included, Coq7, Dmpk, Ccne2, Kras, Wnt2b, Il3raand Tnfrsf10a, and qRT-PCR analysis revealed that Kraswas significantly higher in pituitaries of male 129S6/SvEv mice. Thus, our results demonstrate that Krasand other genes could represent possible genetic modifiers of Men1.

Published
2020
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108. An N‐Ethyl‐N‐Nitrosourea (ENU)‐Induced Tyr265Stop Mutation of the DNA Polymerase Accessory Subunit Gamma 2 (Polg2) Is Associated With Renal Calcification in Mice.

Author

Gorvin, Caroline M, Ahmad, Bushra N, Stechman, Michael J, Loh, Nellie Y, Hough, Tertius A, Leo, Paul, Marshall, Mhairi, Sethi, Siddharth, Bentley, Liz, Piret, Sian E, Reed, Anita, Jeyabalan, Jeshmi, Christie, Paul T, Wells, Sara, Simon, Michelle M, Mallon, Ann‐Marie, Schulz, Herbert, Huebner, Norbert, Brown, Matthew A, and Cox, Roger D

Abstract

Renal calcification (RCALC) resulting in nephrolithiasis and nephrocalcinosis, which affects ∼10% of adults by 70 years of age, involves environmental and genetic etiologies. Thus, nephrolithiasis and nephrocalcinosis occurs as an inherited disorder in ∼65% of patients, and may be associated with endocrine and metabolic disorders including: primary hyperparathyroidism, hypercalciuria, renal tubular acidosis, cystinuria, and hyperoxaluria. Investigations of families with nephrolithiasis and nephrocalcinosis have identified some causative genes, but further progress is limited as large families are unavailable for genetic studies. We therefore embarked on establishing mouse models for hereditary nephrolithiasis and nephrocalcinosis by performing abdominal X‐rays to identify renal opacities in N‐ethyl‐N‐nitrosourea (ENU)‐mutagenized mice. This identified a mouse with RCALC inherited as an autosomal dominant trait, designated RCALC type 2 (RCALC2). Genomewide mapping located the Rcalc2 locus to a ∼16‐Mbp region on chromosome 11D‐E2 and whole‐exome sequence analysis identified a heterozygous mutation in the DNA polymerase gamma‐2, accessory subunit (Polg2) resulting in a nonsense mutation, Tyr265Stop (Y265X), which co‐segregated with RCALC2. Kidneys of mutant mice (Polg2+/Y265X) had lower POLG2 mRNA and protein expression, compared to wild‐type littermates (Polg2+/+). The Polg2+/Y265X and Polg2+/+ mice had similar plasma concentrations of sodium, potassium, calcium, phosphate, chloride, urea, creatinine, glucose, and alkaline phosphatase activity; and similar urinary fractional excretion of calcium, phosphate, oxalate, and protein. Polg2 encodes the minor subunit of the mitochondrial DNA (mtDNA) polymerase and the mtDNA content in Polg2+/Y265X kidneys was reduced compared to Polg2+/+ mice, and cDNA expression profiling revealed differential expression of 26 genes involved in several biological processes including mitochondrial DNA function, apoptosis, and ubiquitination, the complement pathway, and inflammatory pathways. In addition, plasma of Polg2+/Y265X mice, compared to Polg2+/+ littermates had higher levels of reactive oxygen species. Thus, our studies have identified a mutant mouse model for inherited renal calcification associated with a Polg2 nonsense mutation. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Published
2019
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109. A bioimage informatics platform for high-throughput embryo phenotyping

Author

Brown, James M., primary, Horner, Neil R., additional, Lawson, Thomas N., additional, Fiegel, Tanja, additional, Greenaway, Simon, additional, Morgan, Hugh, additional, Ring, Natalie, additional, Santos, Luis, additional, Sneddon, Duncan, additional, Teboul, Lydia, additional, Vibert, Jennifer, additional, Yaikhom, Gagarine, additional, Westerberg, Henrik, additional, and Mallon, Ann-Marie, additional

Published
2016
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110. Correction of the auditory phenotype in C57BL/6N mice via CRISPR/Cas9-mediated homology directed repair

Author

Mianné, Joffrey, primary, Chessum, Lauren, additional, Kumar, Saumya, additional, Aguilar, Carlos, additional, Codner, Gemma, additional, Hutchison, Marie, additional, Parker, Andrew, additional, Mallon, Ann-Marie, additional, Wells, Sara, additional, Simon, Michelle M., additional, Teboul, Lydia, additional, Brown, Steve D. M., additional, and Bowl, Michael R., additional

Published
2016
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111. INFRAFRONTIER-providing mutant mouse resources as research tools for the international scientific community

Author

Meehan, Terrence F., Chen, Chao Kung, Koscielny, Gautier, Relac, Mike, Wilkinson, Phil, Flicek, Paul, Parkinson, Helen, Bottomley, Joanna, Ramirez-Solis, Ramiro, Smedley, Damian, Castro, Ana, Fessele, Sabine, Steinkamp, Ralph, Hagn, Michael, Raess, Michael, De Angelis, Martin Hrabé, Ball, Simon, Blake, Andrew, Fray, Martin, Kenyon, Janet, Mallon, Ann Marie, Brown, Steve, Massimi, Marzia, Matteoni, Raffaele, Tocchini-Valentini, Glauco, Herault, Yann, Kollias, George, Ulfhake, Brun, Demengeot, Jocelyne, Fremond, Cecile, Bosch, Fatima, Montoliu, Lluis, Soininen, Raija, Schughart, Klaus, Brakebusch, Cord, Sedlacek, Radislav, Rülicke, Thomas, McKerlie, Colin, Malissen, Bernard, Iraqi, Fuad, Jonkers, Jos, Russig, Holger, Huylebroeck, Danny, Meehan, Terrence F., Chen, Chao Kung, Koscielny, Gautier, Relac, Mike, Wilkinson, Phil, Flicek, Paul, Parkinson, Helen, Bottomley, Joanna, Ramirez-Solis, Ramiro, Smedley, Damian, Castro, Ana, Fessele, Sabine, Steinkamp, Ralph, Hagn, Michael, Raess, Michael, De Angelis, Martin Hrabé, Ball, Simon, Blake, Andrew, Fray, Martin, Kenyon, Janet, Mallon, Ann Marie, Brown, Steve, Massimi, Marzia, Matteoni, Raffaele, Tocchini-Valentini, Glauco, Herault, Yann, Kollias, George, Ulfhake, Brun, Demengeot, Jocelyne, Fremond, Cecile, Bosch, Fatima, Montoliu, Lluis, Soininen, Raija, Schughart, Klaus, Brakebusch, Cord, Sedlacek, Radislav, Rülicke, Thomas, McKerlie, Colin, Malissen, Bernard, Iraqi, Fuad, Jonkers, Jos, Russig, Holger, and Huylebroeck, Danny

Abstract

The laboratory mouse is a key model organism to investigate mechanism and therapeutics of human disease. The number of targeted genetic mouse models of disease is growing rapidly due to high-throughput production strategies employed by the International Mouse Phenotyping Consortium (IMPC) and the development of new, more efficient genome engineering techniques such as CRISPR based systems. We have previously described the European Mouse Mutant Archive (EMMA) resource and how this international infrastructure provides archiving and distribution worldwide for mutant mouse strains. EMMA has since evolved into INFRAFRONTIER (http://www.infrafrontier.eu), the pan-European research infrastructure for the systemic phenotyping, archiving and distribution of mouse disease models. Here we describe new features including improved search for mouse strains, support for new embryonic stem cell resources, access to training materials via a comprehensive knowledgebase and the promotion of innovative analytical and diagnostic techniques.

Published
2015

112. Organization and evolution of a gene-rich region of the mouse genome: A12.7-Mb region deleted in the Del (13) Svea36H mouse

Author

Mallon, Ann-Marie, Weekes, Joseph, Wilming, Laurens, Gilbert, James G.R., Matthews, Lucy, Peyrefitte, Sandrine, Ashurst, Jennifer, Cadman, Matthews, Botcherby, Marc R.M., Arkell, Ruth, Sellick, Chris A., McKeone, Richard, Strivens, Mark A., Gregory, Simon, Campbell, R. Duncan, Denny, Paul, Brown, Steve D.M., Rogers, Jane, and Hancock, John M.

Subjects
Nucleotide sequence -- Research, Human chromosomes -- Research, Genetic research, Health
Abstract

Del (13) Svea36H (De136H) is a deletion of ~20% of mouse chromosome 13 showing conserved synteny with human chromosome 5p22.1-6p22.3l6p25. 12.7 Mb of finished and annotated sequence from Del136H mouse that provides insights into mouse genome evolution is described.

Published
2004

114. Erratum: Corrigendum: Comparative visualization of genotype-phenotype relationships

Author

Yaikhom, Gagarine, primary, Morgan, Hugh, additional, Sneddon, Duncan, additional, Retha, Ahmad, additional, Atienza-Herrero, Julian, additional, Blake, Andrew, additional, Brown, James, additional, Di Fenza, Armida, additional, Fiegel, Tanja, additional, Horner, Neil, additional, Ring, Natalie, additional, Santos, Luis, additional, Westerberg, Henrik, additional, Brown, Steve D M, additional, and Mallon, Ann-Marie, additional

Published
2015
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115. The digital revolution in phenotyping

Author

Oellrich, Anika, primary, Collier, Nigel, additional, Groza, Tudor, additional, Rebholz-Schuhmann, Dietrich, additional, Shah, Nigam, additional, Bodenreider, Olivier, additional, Boland, Mary Regina, additional, Georgiev, Ivo, additional, Liu, Hongfang, additional, Livingston, Kevin, additional, Luna, Augustin, additional, Mallon, Ann-Marie, additional, Manda, Prashanti, additional, Robinson, Peter N., additional, Rustici, Gabriella, additional, Simon, Michelle, additional, Wang, Liqin, additional, Winnenburg, Rainer, additional, and Dumontier, Michel, additional

Published
2015
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116. Comparative visualization of genotype-phenotype relationships

Author

Yaikhom, Gagarine, primary, Morgan, Hugh, additional, Sneddon, Duncan, additional, Retha, Ahmad, additional, Atienza-Herrero, Julian, additional, Blake, Andrew, additional, Brown, James, additional, Di Fenza, Armida, additional, Fiegel, Tanja, additional, Horner, Neil, additional, Ring, Natalie, additional, Santos, Luis, additional, Westerberg, Henrik, additional, Brown, Steve D M, additional, and Mallon, Ann-Marie, additional

Published
2015
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117. Mouse Phenotype Database Integration Consortium: integration [corrected] of mouse phenome data resources

Author

Hancock, John M, Adams, Niels C, Aidinis, Vassilis, Blake, Andrew, Bogue, Molly, Brown, Steve D M, Chesler, Elissa J, Davidson, Duncan, Duran, Christopher, Eppig, Janan T, Gailus-Durner, Valérie, Gates, Hilary, Gkoutos, Georgios V, Greenaway, Simon, Hrabé de Angelis, Martin, Kollias, George, Leblanc, Sophie, Lee, Kirsty, Lengger, Christoph, Maier, Holger, Mallon, Ann-Marie, Masuya, Hiroshi, Melvin, David G, Müller, Werner, Parkinson, Helen, Proctor, Glenn, Reuveni, Eli, Schofield, Paul, Shukla, Aadya, Smith, Cynthia, Toyoda, Tetsuro, Vasseur, Laurent, Wakana, Shigeharu, Walling, Alison, White, Jacqui, Wood, Joe, and Zouberakis, Michalis

Subjects
Mice, Phenotype, Databases, Genetic, Animals, Mice, Inbred Strains, Genomics, Mice, Mutant Strains
Abstract

Understanding the functions encoded in the mouse genome will be central to an understanding of the genetic basis of human disease. To achieve this it will be essential to be able to characterize the phenotypic consequences of variation and alterations in individual genes. Data on the phenotypes of mouse strains are currently held in a number of different forms (detailed descriptions of mouse lines, first-line phenotyping data on novel mutations, data on the normal features of inbred lines) at many sites worldwide. For the most efficient use of these data sets, we have initiated a process to develop standards for the description of phenotypes (using ontologies) and file formats for the description of phenotyping protocols and phenotype data sets. This process is ongoing and needs to be supported by the wider mouse genetics and phenotyping communities to succeed. We invite interested parties to contact us as we develop this process further.

Published
2007

119. An ENU-induced Tyr265Stop mutation in Polg2 is associated with renal calcification in RCALC2 mice

Author

Gorvin, Caroline, primary, Piret, Sian, additional, Ahmad, Bushra, additional, Stechman, Michael, additional, Loh, Nellie, additional, Hough, Tertius, additional, Leo, Paul, additional, Marshall, Mhairi, additional, Sethi, Siddharth, additional, Bentley, Liz, additional, Reed, Anita, additional, Christie, Paul, additional, Simon, Michelle, additional, Mallon, Ann-Marie, additional, Brown, Matthew, additional, Cox, Roger, additional, Brown, Steve, additional, and Thakker, Rajesh, additional

Published
2014
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120. Unlocking the bottleneck in forward genetics using whole-genome sequencing and identity by descent to isolate causative mutations

Author

Bull, Katherine R, Rimmer, Andrew J, Siggs, Owen M, Miosge, Lisa A, Roots, Carla M, Enders, Anselm, Bertram, Edward M, Crockford, Tanya L, Whittle, Belinda, Potter, Paul K, Simon, Michelle M, Mallon, Ann-Marie, Brown, Steve D M, Beutler, Bruce, Goodnow, Christopher C, Lunter, Gerton, Cornall, Richard J, Bull, Katherine R, Rimmer, Andrew J, Siggs, Owen M, Miosge, Lisa A, Roots, Carla M, Enders, Anselm, Bertram, Edward M, Crockford, Tanya L, Whittle, Belinda, Potter, Paul K, Simon, Michelle M, Mallon, Ann-Marie, Brown, Steve D M, Beutler, Bruce, Goodnow, Christopher C, Lunter, Gerton, and Cornall, Richard J

Abstract

Forward genetics screens with N-ethyl-N-nitrosourea (ENU) provide a powerful way to illuminate gene function and generate mouse models of human disease; however, the identification of causative mutations remains a limiting step. Current strategies depend on conventional mapping, so the propagation of affected mice requires non-lethal screens; accurate tracking of phenotypes through pedigrees is complex and uncertain; out-crossing can introduce unexpected modifiers; and Sanger sequencing of candidate genes is inefficient. Here we show how these problems can be efficiently overcome using whole-genome sequencing (WGS) to detect the ENU mutations and then identify regions that are identical by descent (IBD) in multiple affected mice. In this strategy, we use a modification of the Lander-Green algorithm to isolate causative recessive and dominant mutations, even at low coverage, on a pure strain background. Analysis of the IBD regions also allows us to calculate the ENU mutation rate (1.54 mutations per Mb) and to model future strategies for genetic screens in mice. The introduction of this approach will accelerate the discovery of causal variants, permit broader and more informative lethal screens to be used, reduce animal costs, and herald a new era for ENU mutagenesis.

Published
2013

121. Promoting coherent minimum reporting guidelines for biological and biomedical investigations: the MIBBI project

Author

Taylor, Chris F., Field, Dawn, Sansone, Susanna-Assunta, Aerts, Jan, Apweiler, Rolf, Ashburner, Michael, Ball, Catherine A., Binz, Pierre-Alain, Bogue, Molly, Booth, Tim, Brazma, Alvis, Brinkman, Ryan R., Clark, Adam Michael, Deutsch, Eric W., Fiehn, Oliver, Fostel, Jennifer, Ghazal, Peter, Gibson, Frank, Gray, Tanya, Grimes, Graeme, Hancock, John M., Hardy, Nigel W., Hermjakob, Henning, Julian, Randall K., Kane, Matthew, Kettner, Carsten, Kinsinger, Christopher, Kolker, Eugene, Kuiper, Martin, Le Novere, Nicolas, Leebens-Mack, Jim, Lewis, Suzanna E., Lord, Phillip, Mallon, Ann-Marie, Marthandan, Nishanth, Masuya, Hiroshi, McNally, Ruth, Mehrle, Alexander, Morrison, Norman, Orchard, Sandra, Quackenbush, John, Reecy, James M., Robertson, Donald G., Rocca-Serra, Philippe, Rodriguez, Henry, Rosenfelder, Heiko, Santoyo-Lopez, Javier, Scheuermann, Richard H., Schober, Daniel, Smith, Barry, Snape, Jason, Stoeckert, Christian J., Tipton, Keith, Sterk, Peter, Untergasser, Andreas, Vandesompele, Jo, Wiemann, Stefan, Taylor, Chris F., Field, Dawn, Sansone, Susanna-Assunta, Aerts, Jan, Apweiler, Rolf, Ashburner, Michael, Ball, Catherine A., Binz, Pierre-Alain, Bogue, Molly, Booth, Tim, Brazma, Alvis, Brinkman, Ryan R., Clark, Adam Michael, Deutsch, Eric W., Fiehn, Oliver, Fostel, Jennifer, Ghazal, Peter, Gibson, Frank, Gray, Tanya, Grimes, Graeme, Hancock, John M., Hardy, Nigel W., Hermjakob, Henning, Julian, Randall K., Kane, Matthew, Kettner, Carsten, Kinsinger, Christopher, Kolker, Eugene, Kuiper, Martin, Le Novere, Nicolas, Leebens-Mack, Jim, Lewis, Suzanna E., Lord, Phillip, Mallon, Ann-Marie, Marthandan, Nishanth, Masuya, Hiroshi, McNally, Ruth, Mehrle, Alexander, Morrison, Norman, Orchard, Sandra, Quackenbush, John, Reecy, James M., Robertson, Donald G., Rocca-Serra, Philippe, Rodriguez, Henry, Rosenfelder, Heiko, Santoyo-Lopez, Javier, Scheuermann, Richard H., Schober, Daniel, Smith, Barry, Snape, Jason, Stoeckert, Christian J., Tipton, Keith, Sterk, Peter, Untergasser, Andreas, Vandesompele, Jo, and Wiemann, Stefan

Abstract

The Minimum Information for Biological and Biomedical Investigations (MIBBI) project aims to foster the coordinated development of minimum-information checklists and provide a resource for those exploring the range of extant checklists.

Published
2008

122. The International Mouse Phenotyping Consortium Web Portal, a unified point of access for knockout mice and related phenotyping data

Author

Koscielny, Gautier, primary, Yaikhom, Gagarine, additional, Iyer, Vivek, additional, Meehan, Terrence F., additional, Morgan, Hugh, additional, Atienza-Herrero, Julian, additional, Blake, Andrew, additional, Chen, Chao-Kung, additional, Easty, Richard, additional, Di Fenza, Armida, additional, Fiegel, Tanja, additional, Grifiths, Mark, additional, Horne, Alan, additional, Karp, Natasha A., additional, Kurbatova, Natalja, additional, Mason, Jeremy C., additional, Matthews, Peter, additional, Oakley, Darren J., additional, Qazi, Asfand, additional, Regnart, Jack, additional, Retha, Ahmad, additional, Santos, Luis A., additional, Sneddon, Duncan J., additional, Warren, Jonathan, additional, Westerberg, Henrik, additional, Wilson, Robert J., additional, Melvin, David G., additional, Smedley, Damian, additional, Brown, Steve D. M., additional, Flicek, Paul, additional, Skarnes, William C., additional, Mallon, Ann-Marie, additional, and Parkinson, Helen, additional

Published
2013
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124. Unlocking the Bottleneck in Forward Genetics Using Whole-Genome Sequencing and Identity by Descent to Isolate Causative Mutations

Author

Bull, Katherine R., primary, Rimmer, Andrew J., additional, Siggs, Owen M., additional, Miosge, Lisa A., additional, Roots, Carla M., additional, Enders, Anselm, additional, Bertram, Edward M., additional, Crockford, Tanya L., additional, Whittle, Belinda, additional, Potter, Paul K., additional, Simon, Michelle M., additional, Mallon, Ann-Marie, additional, Brown, Steve D. M., additional, Beutler, Bruce, additional, Goodnow, Christopher C., additional, Lunter, Gerton, additional, and Cornall, Richard J., additional

Published
2013
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125. A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains

Author

Simon, Michelle M, primary, Greenaway, Simon, additional, White, Jacqueline K, additional, Fuchs, Helmut, additional, Gailus-Durner, Valérie, additional, Wells, Sara, additional, Sorg, Tania, additional, Wong, Kim, additional, Bedu, Elodie, additional, Cartwright, Elizabeth J, additional, Dacquin, Romain, additional, Djebali, Sophia, additional, Estabel, Jeanne, additional, Graw, Jochen, additional, Ingham, Neil J, additional, Jackson, Ian J, additional, Lengeling, Andreas, additional, Mandillo, Silvia, additional, Marvel, Jacqueline, additional, Meziane, Hamid, additional, Preitner, Frédéric, additional, Puk, Oliver, additional, Roux, Michel, additional, Adams, David J, additional, Atkins, Sarah, additional, Ayadi, Abdel, additional, Becker, Lore, additional, Blake, Andrew, additional, Brooker, Debra, additional, Cater, Heather, additional, Champy, Marie-France, additional, Combe, Roy, additional, Danecek, Petr, additional, di Fenza, Armida, additional, Gates, Hilary, additional, Gerdin, Anna-Karin, additional, Golini, Elisabetta, additional, Hancock, John M, additional, Hans, Wolfgang, additional, Hölter, Sabine M, additional, Hough, Tertius, additional, Jurdic, Pierre, additional, Keane, Thomas M, additional, Morgan, Hugh, additional, Müller, Werner, additional, Neff, Frauke, additional, Nicholson, George, additional, Pasche, Bastian, additional, Roberson, Laura-Anne, additional, Rozman, Jan, additional, Sanderson, Mark, additional, Santos, Luis, additional, Selloum, Mohammed, additional, Shannon, Carl, additional, Southwell, Anne, additional, Tocchini-Valentini, Glauco P, additional, Vancollie, Valerie E, additional, Westerberg, Henrik, additional, Wurst, Wolfgang, additional, Zi, Min, additional, Yalcin, Binnaz, additional, Ramirez-Solis, Ramiro, additional, Steel, Karen P, additional, Mallon, Ann-Marie, additional, de Angelis, Martin, additional, Herault, Yann, additional, and Brown, Steve DM, additional

Published
2013
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126. The digital revolution in phenotyping.

Author

Oellrich, Anika, Collier, Nigel, Groza, Tudor, Rebholz-Schuhmann, Dietrich, Nigam Shah, Bodenreider, Olivier, Boland, Mary Regina, Georgiev, Ivo, Hongfang Liu, Livingston, Kevin, Luna, Augustin, Mallon, Ann-Marie, Manda, Prashanti, Robinson, Peter N., Rustici, Gabriella, Simon, Michelle, Liqin Wang, Winnenburg, Rainer, and Dumontier, Michel

Subjects
PHENOTYPES, GENETICS, ENTEROTYPES, GENETIC pleiotropy, GENOTYPES
Abstract

Phenotypes have gained increased notoriety in the clinical and biological domain owing to their application in numerous areas such as the discovery of disease genes and drug targets, phylogenetics and pharmacogenomics. Phenotypes, defined as observable characteristics of organisms, can be seen as one of the bridges that lead to a translation of experimental findings into clinical applications and thereby support 'bench to bedside' efforts. However, to build this translational bridge, a common and universal understanding of phenotypes is required that goes beyond domain-specific definitions. To achieve this ambitious goal, a digital revolution is ongoing that enables the encoding of data in computer-readable formats and the data storage in specialized repositories, ready for integration, enabling translational research. While phenome research is an ongoing endeavor, the true potential hidden in the currently available data still needs to be unlocked, offering exciting opportunities for the forthcoming years. Here, we provide insights into the state-of-the-art in digital phenotyping, by means of representing, acquiring and analyzing phenotype data. In addition, we provide visions of this field for future research work that could enable better applications of phenotype data. [ABSTRACT FROM AUTHOR]

Published
2016
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127. Organization and Evolution of a Gene-rich Region of the Mouse Genome: A 12.7Mb Region Deleted in the Del(13) Svea36H Mouse

Author

Mallon, Ann-Marie, Wilming, Laurens, Weekes, Joseph, Gilbert, James G R, Ashurst, Jennifer, Payrefitte, Sandrine, Matthews, Lucy, Cadman, Matthew, McKeone, Richard, Sellick, Chris A, Arkell, Ruth, Botcherby, Marc R M, Strivens, Mark A, Campbell, R Duncan, Gregory, Simon, Denny, Paul, Hancock, John M, Rogers, Jane, Brown, Steve D M, Mallon, Ann-Marie, Wilming, Laurens, Weekes, Joseph, Gilbert, James G R, Ashurst, Jennifer, Payrefitte, Sandrine, Matthews, Lucy, Cadman, Matthew, McKeone, Richard, Sellick, Chris A, Arkell, Ruth, Botcherby, Marc R M, Strivens, Mark A, Campbell, R Duncan, Gregory, Simon, Denny, Paul, Hancock, John M, Rogers, Jane, and Brown, Steve D M

Abstract

Del(13)Svea36H (Del36H) is a deletion of ∼20% of mouse chromosome 13 showing conserved synteny with human chromosome 6p22.1-6p22.3/6p25. The human region is lost in some deletion syndromes and is the site of several disease loci. Heterozygous Del36H mic

Published
2004

128. Anatomy ontologies and potential users: bridging the gap

Author

Travillian, Ravensara S, primary, Adamusiak, Tomasz, additional, Burdett, Tony, additional, Gruenberger, Michael, additional, Hancock, John, additional, Mallon, Ann-Marie, additional, Malone, James, additional, Schofield, Paul, additional, and Parkinson, Helen, additional

Published
2011
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129. EuroPhenome: a repository for high-throughput mouse phenotyping data

Author

Morgan, Hugh, primary, Beck, Tim, additional, Blake, Andrew, additional, Gates, Hilary, additional, Adams, Niels, additional, Debouzy, Guillaume, additional, Leblanc, Sophie, additional, Lengger, Christoph, additional, Maier, Holger, additional, Melvin, David, additional, Meziane, Hamid, additional, Richardson, Dave, additional, Wells, Sara, additional, White, Jacqui, additional, Wood, Joe, additional, de Angelis, Martin Hrabé, additional, Brown, Steve D. M., additional, Hancock, John M., additional, and Mallon, Ann-Marie, additional

Published
2009
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130. MouseBook: an integrated portal of mouse resources

Author

Blake, Andrew, primary, Pickford, Karen, additional, Greenaway, Simon, additional, Thomas, Steve, additional, Pickard, Amanda, additional, Williamson, Christine M., additional, Adams, Niels C., additional, Walling, Alison, additional, Beck, Tim, additional, Fray, Martin, additional, Peters, Jo, additional, Weaver, Tom, additional, Brown, Steve D. M., additional, Hancock, John M., additional, and Mallon, Ann-Marie, additional

Published
2009
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132. Promoting coherent minimum reporting guidelines for biological and biomedical investigations: the MIBBI project

Author

Taylor, Chris F, primary, Field, Dawn, additional, Sansone, Susanna-Assunta, additional, Aerts, Jan, additional, Apweiler, Rolf, additional, Ashburner, Michael, additional, Ball, Catherine A, additional, Binz, Pierre-Alain, additional, Bogue, Molly, additional, Booth, Tim, additional, Brazma, Alvis, additional, Brinkman, Ryan R, additional, Michael Clark, Adam, additional, Deutsch, Eric W, additional, Fiehn, Oliver, additional, Fostel, Jennifer, additional, Ghazal, Peter, additional, Gibson, Frank, additional, Gray, Tanya, additional, Grimes, Graeme, additional, Hancock, John M, additional, Hardy, Nigel W, additional, Hermjakob, Henning, additional, Julian, Randall K, additional, Kane, Matthew, additional, Kettner, Carsten, additional, Kinsinger, Christopher, additional, Kolker, Eugene, additional, Kuiper, Martin, additional, Novère, Nicolas Le, additional, Leebens-Mack, Jim, additional, Lewis, Suzanna E, additional, Lord, Phillip, additional, Mallon, Ann-Marie, additional, Marthandan, Nishanth, additional, Masuya, Hiroshi, additional, McNally, Ruth, additional, Mehrle, Alexander, additional, Morrison, Norman, additional, Orchard, Sandra, additional, Quackenbush, John, additional, Reecy, James M, additional, Robertson, Donald G, additional, Rocca-Serra, Philippe, additional, Rodriguez, Henry, additional, Rosenfelder, Heiko, additional, Santoyo-Lopez, Javier, additional, Scheuermann, Richard H, additional, Schober, Daniel, additional, Smith, Barry, additional, Snape, Jason, additional, Stoeckert, Christian J, additional, Tipton, Keith, additional, Sterk, Peter, additional, Untergasser, Andreas, additional, Vandesompele, Jo, additional, and Wiemann, Stefan, additional

Published
2008
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134. Organization and Evolution of a Gene-Rich Region of the Mouse Genome: A 12.7-Mb Region Deleted in the Del(13)Svea36H Mouse

Author

Mallon, Ann-Marie, primary, Wilming, Laurens, additional, Weekes, Joseph, additional, Gilbert, James G.R., additional, Ashurst, Jennifer, additional, Peyrefitte, Sandrine, additional, Matthews, Lucy, additional, Cadman, Matthew, additional, McKeone, Richard, additional, Sellick, Chris A., additional, Arkell, Ruth, additional, Botcherby, Marc R.M., additional, Strivens, Mark A., additional, Campbell, R. Duncan, additional, Gregory, Simon, additional, Denny, Paul, additional, Hancock, John M., additional, Rogers, Jane, additional, and Brown, Steve D.M., additional

Published
2004
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135. Defects in whirlin, a PDZ domain molecule involved in stereocilia elongation, cause deafness in the whirler mouse and families with DFNB31

Author

Mburu, Philomena, primary, Mustapha, Mirna, additional, Varela, Anabel, additional, Weil, Dominique, additional, El-Amraoui, Aziz, additional, Holme, Ralph H, additional, Rump, Andreas, additional, Hardisty, Rachel E, additional, Blanchard, Stéphane, additional, Coimbra, Roney S, additional, Perfettini, Isabelle, additional, Parkinson, Nick, additional, Mallon, Ann-Marie, additional, Glenister, Pete, additional, Rogers, Mike J, additional, Paige, Adam J, additional, Moir, Lee, additional, Clay, Jo, additional, Rosenthal, Andre, additional, Liu, Xue Zhong, additional, Blanco, Gonzalo, additional, Steel, Karen P, additional, Petit, Christine, additional, and Brown, Steve D M, additional

Published
2003
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137. The gene mutated in bare patches and striated mice encodes a novel 3β-hydroxysteroid dehydrogenase

Author

Liu, Xiao Yu, primary, Dangel, Andrew W., additional, Kelley, Richard I., additional, Zhao, Wei, additional, Denny, Paul, additional, Botcherby, Marc, additional, Cattanach, Bruce, additional, Peters, Jo, additional, Hunsicker, Patricia R., additional, Mallon, Ann-Marie, additional, Strivens, Mark A., additional, Bate, Rachael, additional, Miller, Webb, additional, Rhodes, Michael, additional, Brown, Stephen D.M., additional, and Herman, Gail E., additional

Published
1999
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139. Phenobabelomics--mouse phenotype data resources.

Author

Hancock, John M. and Mallon, Ann-Marie

Subjects
*GENES, *GENOMES, *LABORATORY mice, *PHENOTYPES, *GENETIC mutation, *BIOINFORMATICS
Abstract

An essential aspect to understanding the functional significance of individual genes in the mouse genome is an understanding of the phenotypic consequences of gene mutations. A wide variety of online sites exist that provide different types of phenotypic information on the laboratory mouse. In this review, we describe the major resources that are currently available and discuss some of the bioinformatics requirements that will be necessary to make more seamless searching, comparison and analysis of these various data types possible. [ABSTRACT FROM AUTHOR]

Published
2007

140. What use is the human genome for understanding the mouse?

Author

Denny, Paul, Bate, Rachael, and Mallon, Ann-Marie

Abstract

Having a working draft of the human genome sequence is proving invaluable to mouse genetic and genomic studies, providing a useful stepping-stone towards the finished sequence of the mouse genome.

Published
2001
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141. The Deep Genome Project

Author

Lloyd, K. C. Kent, Adams, David J., Baynam, Gareth, Beaudet, Arthur L., Bosch, Fatima, Boycott, Kym M., Braun, Robert E., Caulfield, Mark, Cohn, Ronald, Dickinson, Mary E., Dobbie, Michael S., Flenniken, Ann M., Flicek, Paul, Galande, Sanjeev, Gao, Xiang, Grobler, Anne, Heaney, Jason D., Herault, Yann, de Angelis, Martin Hrabě, Lupski, James R., Lyonnet, Stanislas, Mallon, Ann-Marie, Mammano, Fabio, MacRae, Calum A., McInnes, Roderick, McKerlie, Colin, Meehan, Terrence F., Murray, Stephen A., Nutter, Lauryl M. J., Obata, Yuichi, Parkinson, Helen, Pepper, Michael S., Sedlacek, Radislav, Seong, Je Kyung, Shiroishi, Toshihiko, Smedley, Damian, Tocchini-Valentini, Glauco, Valle, David, Wang, Chi-Kuang Leo, Wells, Sara, White, Jacqueline, Wurst, Wolfgang, Xu, Ying, and Brown, Steve D. M.

Published
2020
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142. Disease model discovery from 3,328 gene knockouts by The International Mouse Phenotyping Consortium

Author

Meehan, Terrence F, Conte, Nathalie, West, David B, Jacobsen, Julius O, Mason, Jeremy, Warren, Jonathan, Chen, Chao-Kung, Tudose, Ilinca, Relac, Mike, Matthews, Peter, Karp, Natasha, Santos, Luis, Fiegel, Tanja, Ring, Natalie, Westerberg, Henrik, Greenaway, Simon, Sneddon, Duncan, Morgan, Hugh, Codner, Gemma F, Stewart, Michelle E, Brown, James, Horner, Neil, International Mouse Phenotyping Consortium, Haendel, Melissa, Washington, Nicole, Mungall, Christopher J, Reynolds, Corey L, Gallegos, Juan, Gailus-Durner, Valerie, Sorg, Tania, Pavlovic, Guillaume, Bower, Lynette R, Moore, Mark, Morse, Iva, Gao, Xiang, Tocchini-Valentini, Glauco P, Obata, Yuichi, Cho, Soo Young, Seong, Je Kyung, Seavitt, John, Beaudet, Arthur L, Dickinson, Mary E, Herault, Yann, Wurst, Wolfgang, De Angelis, Martin Hrabe, Lloyd, KC Kent, Flenniken, Ann M, Nutter, Lauryl MJ, Newbigging, Susan, McKerlie, Colin, Justice, Monica J, Murray, Stephen A, Svenson, Karen L, Braun, Robert E, White, Jacqueline K, Bradley, Allan, Flicek, Paul, Wells, Sara, Skarnes, William C, Adams, David J, Parkinson, Helen, Mallon, Ann-Marie, Brown, Steve DM, and Smedley, Damian

Subjects
Male, Mice, Knockout, Disease Models, Animal, Gene Knockout Techniques, Mice, Phenotype, Genetic Diseases, Inborn, Animals, Humans, Female, Genetic Predisposition to Disease, 3. Good health
Abstract

Although next-generation sequencing has revolutionized the ability to associate variants with human diseases, diagnostic rates and development of new therapies are still limited by a lack of knowledge of the functions and pathobiological mechanisms of most genes. To address this challenge, the International Mouse Phenotyping Consortium is creating a genome- and phenome-wide catalog of gene function by characterizing new knockout-mouse strains across diverse biological systems through a broad set of standardized phenotyping tests. All mice will be readily available to the biomedical community. Analyzing the first 3,328 genes identified models for 360 diseases, including the first models, to our knowledge, for type C Bernard-Soulier, Bardet-Biedl-5 and Gordon Holmes syndromes. 90% of our phenotype annotations were novel, providing functional evidence for 1,092 genes and candidates in genetically uncharacterized diseases including arrhythmogenic right ventricular dysplasia 3. Finally, we describe our role in variant functional validation with The 100,000 Genomes Project and others.

143. Improving local prevalence estimates of SARS-CoV-2 infections using a causal debiasing framework

Author

Nicholson, George, Lehmann, Brieuc, Padellini, Tullia, Pouwels, Koen B., Jersakova, Radka, Lomax, James, King, Ruairidh E., Mallon, Ann-Marie, Diggle, Peter J., Richardson, Sylvia, Blangiardo, Marta, and Holmes, Chris

Subjects
692/699/255/2514, article, 692/308/174, 3. Good health
Abstract

Funder: Oxford University | Jesus College, University of Oxford; doi: https://doi.org/10.13039/501100000645, Funder: Joint Biosecurity Centre, Global and national surveillance of SARS-CoV-2 epidemiology is mostly based on targeted schemes focused on testing individuals with symptoms. These tested groups are often unrepresentative of the wider population and exhibit test positivity rates that are biased upwards compared with the true population prevalence. Such data are routinely used to infer infection prevalence and the effective reproduction number, Rt, which affects public health policy. Here, we describe a causal framework that provides debiased fine-scale spatiotemporal estimates by combining targeted test counts with data from a randomized surveillance study in the United Kingdom called REACT. Our probabilistic model includes a bias parameter that captures the increased probability of an infected individual being tested, relative to a non-infected individual, and transforms observed test counts to debiased estimates of the true underlying local prevalence and Rt. We validated our approach on held-out REACT data over a 7-month period. Furthermore, our local estimates of Rt are indicative of 1-week- and 2-week-ahead changes in SARS-CoV-2-positive case numbers. We also observed increases in estimated local prevalence and Rt that reflect the spread of the Alpha and Delta variants. Our results illustrate how randomized surveys can augment targeted testing to improve statistical accuracy in monitoring the spread of emerging and ongoing infectious disease.

144. Improving local prevalence estimates of SARS-CoV-2 infections using a causal debiasing framework

Author

Nicholson, George, Lehmann, Brieuc, Padellini, Tullia, Pouwels, Koen B, Jersakova, Radka, Lomax, James, King, Ruairidh E, Mallon, Ann-Marie, Diggle, Peter J, Richardson, Sylvia, Blangiardo, Marta, and Holmes, Chris

Subjects
COVID-19 Testing, Models, Statistical, Spatio-Temporal Analysis, Bias, SARS-CoV-2, Basic Reproduction Number, Prevalence, COVID-19, Humans, Reproducibility of Results, United Kingdom, 3. Good health, Forecasting
Abstract

Funder: Oxford University | Jesus College, University of Oxford, Funder: Joint Biosecurity Centre, Global and national surveillance of SARS-CoV-2 epidemiology is mostly based on targeted schemes focused on testing individuals with symptoms. These tested groups are often unrepresentative of the wider population and exhibit test positivity rates that are biased upwards compared with the true population prevalence. Such data are routinely used to infer infection prevalence and the effective reproduction number, Rt, which affects public health policy. Here, we describe a causal framework that provides debiased fine-scale spatiotemporal estimates by combining targeted test counts with data from a randomized surveillance study in the United Kingdom called REACT. Our probabilistic model includes a bias parameter that captures the increased probability of an infected individual being tested, relative to a non-infected individual, and transforms observed test counts to debiased estimates of the true underlying local prevalence and Rt. We validated our approach on held-out REACT data over a 7-month period. Furthermore, our local estimates of Rt are indicative of 1-week- and 2-week-ahead changes in SARS-CoV-2-positive case numbers. We also observed increases in estimated local prevalence and Rt that reflect the spread of the Alpha and Delta variants. Our results illustrate how randomized surveys can augment targeted testing to improve statistical accuracy in monitoring the spread of emerging and ongoing infectious disease.

145. Improving local prevalence estimates of SARS-CoV-2 infections using a causal debiasing framework

Author

Nicholson, George, Lehmann, Brieuc, Padellini, Tullia, Pouwels, Koen B, Jersakova, Radka, Lomax, James, King, Ruairidh E, Mallon, Ann-Marie, Diggle, Peter J, Richardson, Sylvia, Blangiardo, Marta, and Holmes, Chris

Subjects
692/699/255/2514, article, 692/308/174, 3. Good health
Abstract

Funder: Oxford University | Jesus College, University of Oxford; doi: https://doi.org/10.13039/501100000645, Funder: Joint Biosecurity Centre, Global and national surveillance of SARS-CoV-2 epidemiology is mostly based on targeted schemes focused on testing individuals with symptoms. These tested groups are often unrepresentative of the wider population and exhibit test positivity rates that are biased upwards compared with the true population prevalence. Such data are routinely used to infer infection prevalence and the effective reproduction number, Rt, which affects public health policy. Here, we describe a causal framework that provides debiased fine-scale spatiotemporal estimates by combining targeted test counts with data from a randomized surveillance study in the United Kingdom called REACT. Our probabilistic model includes a bias parameter that captures the increased probability of an infected individual being tested, relative to a non-infected individual, and transforms observed test counts to debiased estimates of the true underlying local prevalence and Rt. We validated our approach on held-out REACT data over a 7-month period. Furthermore, our local estimates of Rt are indicative of 1-week- and 2-week-ahead changes in SARS-CoV-2-positive case numbers. We also observed increases in estimated local prevalence and Rt that reflect the spread of the Alpha and Delta variants. Our results illustrate how randomized surveys can augment targeted testing to improve statistical accuracy in monitoring the spread of emerging and ongoing infectious disease.

146. High-throughput discovery of novel developmental phenotypes

Author

Dickinson, Mary E., Flenniken, Ann M., Ji, Xiao, Teboul, Lydia, Wong, Michael D., White, Jacqueline K., Meehan, Terrence F., Weninger, Wolfgang J., Westerberg, Henrik, Adissu, Hibret, Baker, Candice N., Bower, Lynette, Brown, James M., Caddle, L. Brianna, Chiani, Francesco, Clary, Dave, Cleak, James, Daly, Mark J., Denegre, James M., Doe, Brendan, Dolan, Mary E., Edie, Sarah M., Fuchs, Helmut, Gailus-Durner, Valerie, Galli, Antonella, Gambadoro, Alessia, Gallegos, Juan, Guo, Shiying, Horner, Neil R., Hsu, Chih-Wei, Johnson, Sara J., Kalaga, Sowmya, Keith, Lance C., Lanoue, Louise, Lawson, Thomas N., Lek, Monkol, Mark, Manuel, Marschall, Susan, Mason, Jeremy, McElwee, Melissa L., Newbigging, Susan, Nutter, Lauryl M. J., Peterson, Kevin A., Ramirez-Solis, Ramiro, Rowland, Douglas J., Ryder, Edward, Samocha, Kaitlin E., Seavitt, John R., Selloum, Mohammed, Szoke-Kovacs, Zsombor, Tamura, Masaru, Trainor, Amanda G., Tudose, Ilinca, Wakana, Shigeharu, Warren, Jonathan, Wendling, Olivia, West, David B., Wong, Leeyean, Yoshiki, Atsushi, MacArthur, Daniel G., Tocchini-Valentini, Glauco P., Gao, Xiang, Flicek, Paul, Bradley, Allan, Skarnes, William C., Justice, Monica J., Parkinson, Helen E., Moore, Mark, Wells, Sara, Braun, Robert E., Svenson, Karen L., de Angelis, Martin Hrabe, Herault, Yann, Mohun, Tim, Mallon, Ann-Marie, Henkelman, R. Mark, Brown, Steve D. M., Adams, David J., Lloyd, K. C. Kent, McKerlie, Colin, Beaudet, Arthur L., Bućan, Maja, Murray, Stephen A., Dickinson, Mary E., Flenniken, Ann M., Ji, Xiao, Teboul, Lydia, Wong, Michael D., White, Jacqueline K., Meehan, Terrence F., Weninger, Wolfgang J., Westerberg, Henrik, Adissu, Hibret, Baker, Candice N., Bower, Lynette, Brown, James M., Caddle, L. Brianna, Chiani, Francesco, Clary, Dave, Cleak, James, Daly, Mark J., Denegre, James M., Doe, Brendan, Dolan, Mary E., Edie, Sarah M., Fuchs, Helmut, Gailus-Durner, Valerie, Galli, Antonella, Gambadoro, Alessia, Gallegos, Juan, Guo, Shiying, Horner, Neil R., Hsu, Chih-Wei, Johnson, Sara J., Kalaga, Sowmya, Keith, Lance C., Lanoue, Louise, Lawson, Thomas N., Lek, Monkol, Mark, Manuel, Marschall, Susan, Mason, Jeremy, McElwee, Melissa L., Newbigging, Susan, Nutter, Lauryl M. J., Peterson, Kevin A., Ramirez-Solis, Ramiro, Rowland, Douglas J., Ryder, Edward, Samocha, Kaitlin E., Seavitt, John R., Selloum, Mohammed, Szoke-Kovacs, Zsombor, Tamura, Masaru, Trainor, Amanda G., Tudose, Ilinca, Wakana, Shigeharu, Warren, Jonathan, Wendling, Olivia, West, David B., Wong, Leeyean, Yoshiki, Atsushi, MacArthur, Daniel G., Tocchini-Valentini, Glauco P., Gao, Xiang, Flicek, Paul, Bradley, Allan, Skarnes, William C., Justice, Monica J., Parkinson, Helen E., Moore, Mark, Wells, Sara, Braun, Robert E., Svenson, Karen L., de Angelis, Martin Hrabe, Herault, Yann, Mohun, Tim, Mallon, Ann-Marie, Henkelman, R. Mark, Brown, Steve D. M., Adams, David J., Lloyd, K. C. Kent, McKerlie, Colin, Beaudet, Arthur L., Bućan, Maja, and Murray, Stephen A.

Abstract

Approximately one-third of all mammalian genes are essential for life. Phenotypes resulting from knockouts of these genes in mice have provided tremendous insight into gene function and congenital disorders. As part of the International Mouse Phenotyping Consortium effort to generate and phenotypically characterize 5,000 knockout mouse lines, here we identify 410 lethal genes during the production of the first 1,751 unique gene knockouts. Using a standardized phenotyping platform that incorporates high-resolution 3D imaging, we identify phenotypes at multiple time points for previously uncharacterized genes and additional phenotypes for genes with previously reported mutant phenotypes. Unexpectedly, our analysis reveals that incomplete penetrance and variable expressivity are common even on a defined genetic background. In addition, we show that human disease genes are enriched for essential genes, thus providing a dataset that facilitates the prioritization and validation of mutations identified in clinical sequencing efforts.

147. A bioimage informatics platform for high-throughput embryo phenotyping

Author

Brown, James, Horner, Neil R, Lawson, Thomas N, Fiegel, Tanja, Greenaway, Simon, Morgan, Hugh, Ring, Natalie, Santos, Luis, Sneddon, Duncan, Teboul, Lydia, Vibert, Jennifer, Yaikhom, Gagarine, Westerberg, Henrik, Mallon, Ann-Marie, Brown, James, Horner, Neil R, Lawson, Thomas N, Fiegel, Tanja, Greenaway, Simon, Morgan, Hugh, Ring, Natalie, Santos, Luis, Sneddon, Duncan, Teboul, Lydia, Vibert, Jennifer, Yaikhom, Gagarine, Westerberg, Henrik, and Mallon, Ann-Marie

Abstract

High-throughput phenotyping is a cornerstone of numerous functional genomics projects. In recent years, imaging screens have become increasingly important in understanding gene–phenotype relationships in studies of cells, tissues and whole organisms. Three-dimensional (3D) imaging has risen to prominence in the field of developmental biology for its ability to capture whole embryo morphology and gene expression, as exemplified by the International Mouse Phenotyping Consortium (IMPC). Large volumes of image data are being acquired by multiple institutions around the world that encompass a range of modalities, proprietary software and metadata. To facilitate robust downstream analysis, images and metadata must be standardized to account for these differences. As an open scientific enterprise, making the data readily accessible is essential so that members of biomedical and clinical research communities can study the images for themselves without the need for highly specialized software or technical expertise. In this article, we present a platform of software tools that facilitate the upload, analysis and dissemination of 3D images for the IMPC. Over 750 reconstructions from 80 embryonic lethal and subviable lines have been captured to date, all of which are openly accessible at mousephenotype.org. Although designed for the IMPC, all software is available under an open-source licence for others to use and develop further. Ongoing developments aim to increase throughput and improve the analysis and dissemination of image data. Furthermore, we aim to ensure that images are searchable so that users can locate relevant images associated with genes, phenotypes or human diseases of interest.

148. Disease model discovery from 3,328 gene knockouts by The International Mouse Phenotyping Consortium

Author

Meehan, Terrence F, Conte, Nathalie, West, David B, Jacobsen, Julius O, Mason, Jeremy, Warren, Jonathan, Chen, Chao-Kung, Tudose, Ilinca, Relac, Mike, Matthews, Peter, Karp, Natasha, Santos, Luis, Fiegel, Tanja, Ring, Natalie, Westerberg, Henrik, Greenaway, Simon, Sneddon, Duncan, Morgan, Hugh, Codner, Gemma F, Stewart, Michelle E, Brown, James M, Horner, Neil, International Mouse Phenotyping Consortium, The, Haendel, Melissa, Washington, Nicole, Mungall, Christopher J, Reynolds, Corey L, Gallegos, Juan, Gailus-Durner, Valerie, Sorg, Tania, Pavlovic, Guillaume, Bower, Lynette R, Moore, Mark, Morse, Iva, Gao, Xiang, Tocchini-Valentini, Glauco P, Obata, Yuichi, Cho, Soo Young, Seong, Je Kyung, Seavitt, John, Beaudet, Arthur L, Dickinson, Mary E, Herault, Yann, Wurst, Wolfgang, Hrabe de Angelis, Martin, Lloyd, K C Kent, Flenniken, Ann M, Nutter, Lauryl M J, Newbigging, Susan, McKerlie, Colin, Justice, Monica J, Murray, Stephen A, Svenson, Karen L, Braun, Robert E, White, Jacqueline K, Bradley, Allan, Flicek, Paul, Wells, Sara, Skarnes, William C, Adams, David J, Parkinson, Helen, Mallon, Ann-Marie, Brown, Stephen D M, Smedley, Damian, Meehan, Terrence F, Conte, Nathalie, West, David B, Jacobsen, Julius O, Mason, Jeremy, Warren, Jonathan, Chen, Chao-Kung, Tudose, Ilinca, Relac, Mike, Matthews, Peter, Karp, Natasha, Santos, Luis, Fiegel, Tanja, Ring, Natalie, Westerberg, Henrik, Greenaway, Simon, Sneddon, Duncan, Morgan, Hugh, Codner, Gemma F, Stewart, Michelle E, Brown, James M, Horner, Neil, International Mouse Phenotyping Consortium, The, Haendel, Melissa, Washington, Nicole, Mungall, Christopher J, Reynolds, Corey L, Gallegos, Juan, Gailus-Durner, Valerie, Sorg, Tania, Pavlovic, Guillaume, Bower, Lynette R, Moore, Mark, Morse, Iva, Gao, Xiang, Tocchini-Valentini, Glauco P, Obata, Yuichi, Cho, Soo Young, Seong, Je Kyung, Seavitt, John, Beaudet, Arthur L, Dickinson, Mary E, Herault, Yann, Wurst, Wolfgang, Hrabe de Angelis, Martin, Lloyd, K C Kent, Flenniken, Ann M, Nutter, Lauryl M J, Newbigging, Susan, McKerlie, Colin, Justice, Monica J, Murray, Stephen A, Svenson, Karen L, Braun, Robert E, White, Jacqueline K, Bradley, Allan, Flicek, Paul, Wells, Sara, Skarnes, William C, Adams, David J, Parkinson, Helen, Mallon, Ann-Marie, Brown, Stephen D M, and Smedley, Damian

Abstract

Although next-generation sequencing has revolutionized the ability to associate variants with human diseases, diagnostic rates and development of new therapies are still limited by a lack of knowledge of the functions and pathobiological mechanisms of most genes. To address this challenge, the International Mouse Phenotyping Consortium is creating a genome- and phenome-wide catalog of gene function by characterizing new knockout-mouse strains across diverse biological systems through a broad set of standardized phenotyping tests. All mice will be readily available to the biomedical community. Analyzing the first 3,328 genes identified models for 360 diseases, including the first models, to our knowledge, for type C Bernard–Soulier, Bardet–Biedl-5 and Gordon Holmes syndromes. 90% of our phenotype annotations were novel, providing functional evidence for 1,092 genes and candidates in genetically uncharacterized diseases including arrhythmogenic right ventricular dysplasia 3. Finally, we describe our role in variant functional validation with The 100,000 Genomes Project and others.

149. Comparative visualization of genotype-phenotype relationships

Author

Yaikhom, Gagarine, Morgan, Hugh, Sneddon, Duncan, Retha, Ahmad, Atienza-Herrero, Julian, Blake, Andrew, Brown, James, Di Fenza, Armida, Fiegel, Tanja, Horner, Neil, Ring, Natalie, Santos, Luis, Westerberg, Henrik, Brown, Steve DM, Mallon, Ann-Marie, Yaikhom, Gagarine, Morgan, Hugh, Sneddon, Duncan, Retha, Ahmad, Atienza-Herrero, Julian, Blake, Andrew, Brown, James, Di Fenza, Armida, Fiegel, Tanja, Horner, Neil, Ring, Natalie, Santos, Luis, Westerberg, Henrik, Brown, Steve DM, and Mallon, Ann-Marie

Abstract

N/A

150. Disease model discovery from 3,328 gene knockouts by The International Mouse Phenotyping Consortium

Author

Meehan, Terrence F, Conte, Nathalie, West, David B, Jacobsen, Julius O, Mason, Jeremy, Warren, Jonathan, Chen, Chao-Kung, Tudose, Ilinca, Relac, Mike, Matthews, Peter, Karp, Natasha, Santos, Luis, Fiegel, Tanja, Ring, Natalie, Westerberg, Henrik, Greenaway, Simon, Sneddon, Duncan, Morgan, Hugh, Codner, Gemma F, Stewart, Michelle E, Brown, James, Horner, Neil, Haendel, Melissa, Washington, Nicole, Mungall, Christopher J, Reynolds, Corey L, Gallegos, Juan, Gailus-Durner, Valerie, Sorg, Tania, Pavlovic, Guillaume, Bower, Lynette R, Moore, Mark, Morse, Iva, Gao, Xiang, Tocchini-Valentini, Glauco P, Obata, Yuichi, Cho, Soo Young, Seong, Je Kyung, Seavitt, John, Beaudet, Arthur L, Dickinson, Mary E, Herault, Yann, Wurst, Wolfgang, de Angelis, Martin Hrabe, Lloyd, K C Kent, Flenniken, Ann M, Nutter, Lauryl M J, Newbigging, Susan, McKerlie, Colin, Justice, Monica J, Murray, Stephen A, Svenson, Karen L, Braun, Robert E, White, Jacqueline K, Bradley, Allan, Flicek, Paul, Wells, Sara, Skarnes, William C, Adams, David J, Parkinson, Helen, Mallon, Ann-Marie, Brown, Steve D M, Smedley, Damian, Meehan, Terrence F, Conte, Nathalie, West, David B, Jacobsen, Julius O, Mason, Jeremy, Warren, Jonathan, Chen, Chao-Kung, Tudose, Ilinca, Relac, Mike, Matthews, Peter, Karp, Natasha, Santos, Luis, Fiegel, Tanja, Ring, Natalie, Westerberg, Henrik, Greenaway, Simon, Sneddon, Duncan, Morgan, Hugh, Codner, Gemma F, Stewart, Michelle E, Brown, James, Horner, Neil, Haendel, Melissa, Washington, Nicole, Mungall, Christopher J, Reynolds, Corey L, Gallegos, Juan, Gailus-Durner, Valerie, Sorg, Tania, Pavlovic, Guillaume, Bower, Lynette R, Moore, Mark, Morse, Iva, Gao, Xiang, Tocchini-Valentini, Glauco P, Obata, Yuichi, Cho, Soo Young, Seong, Je Kyung, Seavitt, John, Beaudet, Arthur L, Dickinson, Mary E, Herault, Yann, Wurst, Wolfgang, de Angelis, Martin Hrabe, Lloyd, K C Kent, Flenniken, Ann M, Nutter, Lauryl M J, Newbigging, Susan, McKerlie, Colin, Justice, Monica J, Murray, Stephen A, Svenson, Karen L, Braun, Robert E, White, Jacqueline K, Bradley, Allan, Flicek, Paul, Wells, Sara, Skarnes, William C, Adams, David J, Parkinson, Helen, Mallon, Ann-Marie, Brown, Steve D M, and Smedley, Damian

Abstract

Although next-generation sequencing has revolutionized the ability to associate variants with human diseases, diagnostic rates and development of new therapies are still limited by a lack of knowledge of the functions and pathobiological mechanisms of most genes. To address this challenge, the International Mouse Phenotyping Consortium is creating a genome- and phenome-wide catalog of gene function by characterizing new knockout-mouse strains across diverse biological systems through a broad set of standardized phenotyping tests. All mice will be readily available to the biomedical community. Analyzing the first 3,328 genes identified models for 360 diseases, including the first models, to our knowledge, for type C Bernard–Soulier, Bardet–Biedl-5 and Gordon Holmes syndromes. 90% of our phenotype annotations were novel, providing functional evidence for 1,092 genes and candidates in genetically uncharacterized diseases including arrhythmogenic right ventricular dysplasia 3. Finally, we describe our role in variant functional validation with The 100,000 Genomes Project and others.

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