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2. Genotype–phenotype correlations for COL4A3–COL4A5 variants resulting in Gly substitutions in Alport syndrome

Author

Gibson, Joel T., Huang, Mary, Shenelli Croos Dabrera, Marina, Shukla, Krushnam, Rothe, Hansjörg, Hilbert, Pascale, Deltas, Constantinos, Storey, Helen, Lipska-Ziętkiewicz, Beata S., Chan, Melanie M. Y., Sadeghi-Alavijeh, Omid, Gale, Daniel P., Ambrose, J. C., Arumugam, P., Baple, E. L., Bleda, M., Boardman-Pretty, F., Boissiere, J. M., Boustred, C. R., Brittain, H., Caulfield, M. J., Chan, G. C., Craig, C. E. H., Daugherty, L. C., de Burca, A., Devereau, A., Elgar, G., Foulger, R. E., Fowler, T., Furió-Tarí, P., Giess, A., Hackett, J. M., Halai, D., Hamblin, A., Henderson, S., Holman, J. E., Hubbard, T. J. P., Ibáñez, K., Jackson, R., Jones, L. J., Kasperaviciute, D., Kayikci, M., Kousathanas, A., Lahnstein, L., Lawson, K., Leigh, S. E. A., Leong, I. U. S., Lopez, F. J., Maleady-Crowe, F., Mason, J., McDonagh, E. M., Moutsianas, L., Mueller, M., Murugaesu, N., Need, A. C., Odhams, C. A., Orioli, A., Patch, C., Perez-Gil, D., Pereira, M. B., Polychronopoulos, D., Pullinger, J., Rahim, T., Rendon, A., Riesgo-Ferreiro, P., Rogers, T., Ryten, M., Savage, K., Sawant, K., Scott, R. H., Siddiq, A., Sieghart, A., Smedley, D., Smith, K. R., Smith, S. C., Sosinsky, A., Spooner, W., Stevens, H. E., Stuckey, A., Sultana, R., Tanguy, M., Thomas, E. R. A., Thompson, S. R., Tregidgo, C., Tucci, A., Walsh, E., Watters, S. A., Welland, M. J., Williams, E., Witkowska, K., Wood, S. M., Zarowiecki, M., Cerkauskaite, Agne, and Savige, Judy

Subjects
Multidisciplinary, otorhinolaryngologic diseases, urologic and male genital diseases, female genital diseases and pregnancy complications
Abstract

Alport syndrome is the commonest inherited kidney disease and nearly half the pathogenic variants in the COL4A3–COL4A5 genes that cause Alport syndrome result in Gly substitutions. This study examined the molecular characteristics of Gly substitutions that determine the severity of clinical features. Pathogenic COL4A5 variants affecting Gly in the Leiden Open Variation Database in males with X-linked Alport syndrome were correlated with age at kidney failure (n = 157) and hearing loss diagnosis (n = 80). Heterozygous pathogenic COL4A3 and COL4A4 variants affecting Gly (n = 304) in autosomal dominant Alport syndrome were correlated with the risk of haematuria in the UK 100,000 Genomes Project. Gly substitutions were stratified by exon location (1 to 20 or 21 to carboxyl terminus), being adjacent to a non-collagenous region (interruption or terminus), and the degree of instability caused by the replacement residue. Pathogenic COL4A5 variants that resulted in a Gly substitution with a highly destabilising residue reduced the median age at kidney failure by 7 years (p = 0.002), and age at hearing loss diagnosis by 21 years (p = 0.004). Substitutions adjacent to a non-collagenous region delayed kidney failure by 19 years (p = 0.014). Heterozygous pathogenic COL4A3 and COL4A4 variants that resulted in a Gly substitution with a highly destabilising residue (Arg, Val, Glu, Asp, Trp) were associated with an increased risk of haematuria (p = 0.018), and those adjacent to a non-collagenous region were associated with a reduced risk (p = 0.046). Exon location had no effect. In addition, COL4A5 variants adjacent to non-collagenous regions were over-represented in the normal population in gnomAD (p

Published
2022
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3. Heterozygous UCHL1 loss-of-function variants cause a neurodegenerative disorder with spasticity, ataxia, neuropathy, and optic atrophy

Author

Park, Joohyun, Tucci, Arianna, Cali, Elisa, Ryten, M., Savage, K., Sawant, K., Scott, R. H., Siddiq, A., Sieghart, A., Smedley, D., Smith, K. R., Sosinsky, A., Spooner, W., Vestito, Letizia, Stevens, H. E., Stuckey, A., Sultana, R., Thomas, E. R. A., Thompson, S. R., Tregidgo, C., Tucci, A., Walsh, E., Watters, S. A., Welland, M. J., Maroofian, Reza, Williams, E., Witkowska, K., Wood, S. M., Zarowiecki, M., Deininger, Natalie, Rautenberg, Maren, Admard, Jakob, Hahn, Gesa-Astrid, Bartels, Claudius, van Os, Nienke J H, Horvath, Rita, Cipriani, Valentina, Chinnery, Patrick F, Tiet, May Yung, Hewamadduma, Channa, Hadjivassiliou, Marios, Tofaris, George K, Consortium, Genomics England Research, Wood, Nicholas W, Hayer, Stefanie N, Bender, Friedemann, Menden, Benita, Demidov, German, Cordts, Isabell, Klein, Katrin, Nguyen, Huu Phuc, Krauss, Joachim K, Blahak, Christian, Strom, Tim M, Sturm, Marc, van de Warrenburg, Bart, Lerche, Holger, Maček, Boris, Rocca, Clarissa, Synofzik, Matthis, Ossowski, Stephan, Timmann, Dagmar, Wolf, Marc E, Smedley, Damian, Riess, Olaf, Schöls, Ludger, Houlden, Henry, Haack, Tobias B, Hengel, Holger, Senderek, Jan, Ambrose, J. C., Arumugam, P., Baple, E. L., Bleda, M., Boardman-Pretty, F., Boissiere, J. M., Boustred, C. R., Brittain, H., Caulfield, M. J., Chan, G. C., Butryn, Michaela, Craig, C. E. H., Daugherty, L. C., de Burca, A., Devereau, A., Elgar, G., Foulger, R. E., Fowler, T., Furió-Tarí, P., Hackett, J. M., Halai, D., Velic, Ana, Hamblin, A., Henderson, S., Holman, J. E., Hubbard, T. J. P., Ibáñez, K., Jackson, R., Jones, L. J., Kasperaviciute, D., Kayikci, M., Lahnstein, L., Lam, Tanya, Lawson, K., Leigh, S. E. A., Leong, I. U. S., Lopez, F. J., Maleady-Crowe, F., Mason, J., McDonagh, E. M., Moutsianas, L., Mueller, M., Murugaesu, N., Galanaki, Evangelia, Need, A. C., Odhams, C. A., Patch, C., Perez-Gil, D., Polychronopoulos, D., Pullinger, J., Rahim, T., Rendon, A., Riesgo-Ferreiro, P., and Rogers, T.

Subjects
Proteomics, Cerebellar Ataxia, Medizin, genetics [Muscle Spasticity], UCHL1, genetics [Optic Atrophy], genetics [Ubiquitin Thiolesterase], All institutes and research themes of the Radboud University Medical Center, Loss of Function Mutation, Gene burden, genetics [Spastic Paraplegia, Hereditary], Spinocerebellar Ataxias, Humans, ddc:610, genetics [Spinocerebellar Ataxias], Genetics (clinical), genetics [Cerebellar Ataxia], Spastic Paraplegia, Hereditary, Spastic ataxia, genetics [Ataxia], Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Pedigree, Optic Atrophy, Muscle Spasticity, Mutation, Ataxia, Ubiquitin Thiolesterase
Abstract

Purpose Biallelic variants in UCHL1 have been associated with a progressive early-onset neurodegenerative disorder, autosomal recessive spastic paraplegia type 79. In this study, we investigated heterozygous UCHL1 variants on the basis of results from cohort-based burden analyses. Methods Gene-burden analyses were performed on exome and genome data of independent cohorts of patients with hereditary ataxia and spastic paraplegia from Germany and the United Kingdom in a total of 3169 patients and 33,141 controls. Clinical data of affected individuals and additional independent families were collected and evaluated. Patients’ fibroblasts were used to perform mass spectrometry-based proteomics. Results UCHL1 was prioritized in both independent cohorts as a candidate gene for an autosomal dominant disorder. We identified a total of 34 cases from 18 unrelated families, carrying 13 heterozygous loss-of-function variants (15 families) and an inframe insertion (3 families). Affected individuals mainly presented with spasticity (24/31), ataxia (28/31), neuropathy (11/21), and optic atrophy (9/17). The mass spectrometry-based proteomics showed approximately 50% reduction of UCHL1 expression in patients’ fibroblasts. Conclusion Our bioinformatic analysis, in-depth clinical and genetic workup, and functional studies established haploinsufficiency of UCHL1 as a novel disease mechanism in spastic ataxia.

Published
2022
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4. Human and mouse essentiality screens as a resource for disease gene discovery

Author

Cacheiro, Pilar, Muñoz-Fuentes, Violeta, Westerberg, Henrik, Scott, R. H., Siddiq, A., Sieghart, A., Smith, K. R., Sosinsky, A., Spooner, W., Stevens, H. E., Stuckey, A., Sultana, R., Thomas, E. R. A., Konopka, Tomasz, Thompson, S. R., Tregidgo, C., Tucci, A., Walsh, E., Watters, S. A., Welland, M. J., Williams, E., Witkowska, K., Wood, S. M., Zarowiecki, M., Hsu, Chih-Wei, Marschall, Susan, Lengger, Christoph, Maier, Holger, Seisenberger, Claudia, Bürger, Antje, Kühn, Ralf, Schick, Joel, Hörlein, Andreas, Oritz, Oskar, Giesert, Florian, Christiansen, Audrey, Beig, Joachim, Kenyon, Janet, Codner, Gemma, Fray, Martin, Johnson, Sara J, Cleak, James, Szoke-Kovacs, Zsombor, Lafont, David, Vancollie, Valerie E, McLaren, Robbie S B, Lanza, Denise G, Hughes-Hallett, Lena, Rowley, Christine, Sanderson, Emma, Galli, Antonella, Tuck, Elizabeth, Green, Angela, Tudor, Catherine, Siragher, Emma, Dabrowska, Monika, Mazzeo, Cecilia Icoresi, Beaudet, Arthur L, Griffiths, Mark, Gannon, David, Doe, Brendan, Cockle, Nicola, Kirton, Andrea, Bottomley, Joanna, Ingle, Catherine, Ryder, Edward, Gleeson, Diane, Ramirez-Solis, Ramiro, Heaney, Jason D, Birling, Marie-Christine, Pavlovic, Guillaume, Ayadi, Abdel, Hamid, Meziane, About, Ghina Bou, Champy, Marie-France, Jacobs, Hugues, Wendling, Olivia, Leblanc, Sophie, Vasseur, Laurent, Fuchs, Helmut, Chesler, Elissa J, Kumar, Vivek, White, Jacqueline K, Svenson, Karen L, Wiegand, Jean-Paul, Anderson, Laura L, Wilcox, Troy, Clark, James, Ryan, Jennifer, Denegre, James, Gailus-Durner, Valerie, Stearns, Tim, Philip, Vivek, Witmeyer, Catherine, Bates, Lindsay, Seavey, Zachary, Stanley, Pamela, Willet, Amelia, Roper, Willson, Creed, Julie, Moore, Michayla, Sorg, Tania, Dorr, Alex, Fraungruber, Pamelia, Presby, Rose, Mckay, Matthew, Nguyen-Bresinsky, Dong, Goodwin, Leslie, Urban, Rachel, Kane, Coleen, Murray, Stephen A, Prochazka, Jan, Novosadova, Vendula, Lelliott, Christopher J, Wardle-Jones, Hannah, Wells, Sara, Teboul, Lydia, Cater, Heather, Stewart, Michelle, Hough, Tertius, Wurst, Wolfgang, Dickinson, Mary E, Sedlacek, Radislav, Adams, David J, Seavitt, John R, Tocchini-Valentini, Glauco, Mammano, Fabio, Braun, Robert E, McKerlie, Colin, Herault, Yann, de Angelis, Martin Hrabě, Mallon, Ann-Marie, Bucan, Maja, Lloyd, K C Kent, Brown, Steve D M, Parkinson, Helen, Meehan, Terrence F, Smedley, Damian, Consortium, Genomics England Research, Consortium, International Mouse Phenotyping, Ambrose, J. C., Arumugam, P., Baple, E. L., Nutter, Lauryl M J, Bleda, M., Boardman-Pretty, F., Boissiere, J. M., Boustred, C. R., Brittain, H., Caulfield, M. J., Chan, G. C., Craig, C. E. H., Daugherty, L. C., de Burca, A., Peterson, Kevin A, Devereau, A., Elgar, G., Foulger, R. E., Fowler, T., Furió-Tarí, P., Hackett, J. M., Halai, D., Hamblin, A., Henderson, S., Holman, J. E., Haselimashhadi, Hamed, Hubbard, T. J. P., Ibáñez, K., Jackson, R., Jones, L. J., Kasperaviciute, D., Kayikci, M., Lahnstein, L., Lawson, K., Leigh, S. E. A., Leong, I. U. S., Flenniken, Ann M, Lopez, F. J., Maleady-Crowe, F., Mason, J., McDonagh, E. M., Moutsianas, L., Mueller, M., Murugaesu, N., Need, A. C., Odhams, C. A., Patch, C., Morgan, Hugh, Perez-Gil, D., Polychronopoulos, D., Pullinger, J., Rahim, T., Rendon, A., Riesgo-Ferreiro, P., Rogers, T., Ryten, M., Savage, K., Sawant, K., Cacheiro, Pilar [0000-0002-6335-8208], Muñoz-Fuentes, Violeta [0000-0003-3574-546X], Nutter, Lauryl MJ [0000-0001-9619-146X], Peterson, Kevin A [0000-0001-8353-3694], Haselimashhadi, Hamed [0000-0001-7334-2421], Konopka, Tomasz [0000-0003-3042-4712], Hsu, Chih-Wei [0000-0002-9591-9567], Lanza, Denise G [0000-0001-8750-6933], Heaney, Jason D [0000-0001-8475-8828], Fuchs, Helmut [0000-0002-5143-2677], Gailus-Durner, Valerie [0000-0002-6076-0111], Lelliott, Christopher J [0000-0001-8087-4530], Adams, David J [0000-0001-9490-0306], Mammano, Fabio [0000-0003-3751-1691], McKerlie, Colin [0000-0002-2232-0967], Herault, Yann [0000-0001-7049-6900], de Angelis, Martin Hrabě [0000-0002-7898-2353], Lloyd, KC Kent [0000-0002-5318-4144], Smedley, Damian [0000-0002-5836-9850], Apollo - University of Cambridge Repository, Queen Mary University of London (QMUL), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, The Jackson Laboratory [Bar Harbor] (JAX), Baylor College of Medicine (BCM), Baylor University, University of Pennsylvania, The Hospital for sick children [Toronto] (SickKids), Mount Sinai Hospital [Toronto, Canada] (MSH), MRC Harwell Institute [UK], Helmholtz Zentrum München = German Research Center for Environmental Health, Institut Clinique de la Souris (ICS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), French National Infrastructure for Mouse Phenogenomics (PHENOMIN), Institute of Molecular Genetics of the Czech Academy of Sciences (IMG / CAS), Czech Academy of Sciences [Prague] (CAS), The Wellcome Trust Sanger Institute [Cambridge], Technische Universität München = Technical University of Munich (TUM), Ludwig-Maximilians-Universität München (LMU), CNR - Italian National Research Council (CNR), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), German Center for Diabetes Research - Deutsches Zentrum für Diabetesforschung [Neuherberg] (DZD), University of California [Davis] (UC Davis), University of California (UC), J C Ambrose, P Arumugam, E L Baple, M Bleda, F Boardman-Pretty, J M Boissiere, C R Boustred, H Brittain, M J Caulfield, G C Chan, C E H Craig, L C Daugherty, A de Burca, A Devereau, G Elgar, R E Foulger, T Fowler, P Furió-Tarí, J M Hackett, D Halai, A Hamblin, S Henderson, J E Holman, T J P Hubbard, K Ibáñez, R Jackson, L J Jones, D Kasperaviciute, M Kayikci, L Lahnstein, K Lawson, S E A Leigh, I U S Leong, F J Lopez, F Maleady-Crowe, J Mason, E M McDonagh, L Moutsianas, M Mueller, N Murugaesu, A C Need, C A Odhams, C Patch, D Perez-Gil, D Polychronopoulos, J Pullinger, T Rahim, A Rendon, P Riesgo-Ferreiro, T Rogers, M Ryten, K Savage, K Sawant, R H Scott, A Siddiq, A Sieghart, K R Smith, A Sosinsky, W Spooner, H E Stevens, A Stuckey, R Sultana, E R A Thomas, S R Thompson, C Tregidgo, A Tucci, E Walsh, S A Watters, M J Welland, E Williams, K Witkowska, S M Wood, M Zarowiecki, Susan Marschall, Christoph Lengger, Holger Maier, Claudia Seisenberger, Antje Bürger, Ralf Kühn, Joel Schick, Andreas Hörlein, Oskar Oritz, Florian Giesert, Joachim Beig, Janet Kenyon, Gemma Codner, Martin Fray, Sara J Johnson, James Cleak, Zsombor Szoke-Kovacs, David Lafont, Valerie E Vancollie, Robbie S B McLaren, Lena Hughes-Hallett, Christine Rowley, Emma Sanderson, Antonella Galli, Elizabeth Tuck, Angela Green, Catherine Tudor, Emma Siragher, Monika Dabrowska, Cecilia Icoresi Mazzeo, Mark Griffiths, David Gannon, Brendan Doe, Nicola Cockle, Andrea Kirton, Joanna Bottomley, Catherine Ingle, Edward Ryder, Diane Gleeson, Ramiro Ramirez-Solis, Marie-Christine Birling, Guillaume Pavlovic, Abdel Ayadi, Meziane Hamid, Ghina Bou About, Marie-France Champy, Hugues Jacobs, Olivia Wendling, Sophie Leblanc, Laurent Vasseur, Elissa J Chesler, Vivek Kumar, Jacqueline K White, Karen L Svenson, Jean-Paul Wiegand, Laura L Anderson, Troy Wilcox, James Clark, Jennifer Ryan, James Denegre, Tim Stearns, Vivek Philip, Catherine Witmeyer, Lindsay Bates, Zachary Seavey, Pamela Stanley, Amelia Willet, Willson Roper, Julie Creed, Michayla Moore, Alex Dorr, Pamelia Fraungruber, Rose Presby, Matthew Mckay, Dong Nguyen-Bresinsky, Leslie Goodwin, Rachel Urban, Coleen Kane, Herault, Yann, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)

Subjects
0301 basic medicine, Mutation rate, Cancer Research, [SDV]Life Sciences [q-bio], General Physics and Astronomy, methods [Genetic Association Studies], Disease, VARIANTS, Mice, Essential, 0302 clinical medicine, IMPC, Genetics research, Lethal allele, 2.1 Biological and endogenous factors, Aetiology, lcsh:Science, Organism, ComputingMilieux_MISCELLANEOUS, Disease gene, Mice, Knockout, 0303 health sciences, Multidisciplinary, Genes, Essential, genetics [Disease], Genomics, R/BIOCONDUCTOR PACKAGE, DATABASE, UPDATE, GENOME, [SDV] Life Sciences [q-bio], Knockout mouse, Identification (biology), ddc:500, International Mouse Phenotyping Consortium, Technology Platforms, Biotechnology, Knockout, Science, Computational biology, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Genetics, medicine, Animals, Humans, Genetic variation, Clinical genetics, Gene, Genetic Association Studies, 030304 developmental biology, Disease model, Prevention, Human Genome, General Chemistry, medicine.disease, Developmental disorder, Good Health and Well Being, 030104 developmental biology, Genomics England Research Consortium, Genes, lcsh:Q, Generic health relevance, 030217 neurology & neurosurgery, Rare disease
Abstract

The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery., Discovery of causal variants for monogenic disorders has been facilitated by whole exome and genome sequencing, but does not provide a diagnosis for all patients. Here, the authors propose a Full Spectrum of Intolerance to Loss-of-Function (FUSIL) categorization that integrates gene essentiality information to aid disease gene discovery.

Published
2020
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5. Mutational signature in colorectal cancer caused by genotoxic pks+ E. coli

Author

Pleguezuelos-Manzano, Cayetano, Puschhof, Jens, Rosendahl Huber, Axel, van Hoeck, Arne, Wood, Henry M., Nomburg, Jason, Gurjao, Carino, Manders, Freek, Dalmasso, Guillaume, Stege, Paul B., Paganelli, Fernanda L., Geurts, Maarten H., Beumer, Joep, Mizutani, Tomohiro, Miao, Yi, van der Linden, Reinier, van der Elst, Stefan, Ambrose, J. C., Arumugam, P., Baple, E. L., Bleda, M., Boardman-Pretty, F., Boissiere, J. M., Boustred, C. R., Brittain, H., Caulfield, M. J., Chan, G. C., Craig, C. E. H., Daugherty, L. C., de Burca, A., Devereau, A., Elgar, G., Foulger, R. E., Fowler, T., Furió-Tarí, P., Hackett, J. M., Halai, D., Hamblin, A., Henderson, S., Holman, J. E., Hubbard, T. J. P., Ibáñez, K., Jackson, R., Jones, L. J., Kasperaviciute, D., Kayikci, M., Lahnstein, L., Lawson, L., Leigh, S. E. A., Leong, I. U. S., Pleguezuelos-Manzano, Cayetano, Puschhof, Jens, Rosendahl Huber, Axel, van Hoeck, Arne, Wood, Henry M., Nomburg, Jason, Gurjao, Carino, Manders, Freek, Dalmasso, Guillaume, Stege, Paul B., Paganelli, Fernanda L., Geurts, Maarten H., Beumer, Joep, Mizutani, Tomohiro, Miao, Yi, van der Linden, Reinier, van der Elst, Stefan, Ambrose, J. C., Arumugam, P., Baple, E. L., Bleda, M., Boardman-Pretty, F., Boissiere, J. M., Boustred, C. R., Brittain, H., Caulfield, M. J., Chan, G. C., Craig, C. E. H., Daugherty, L. C., de Burca, A., Devereau, A., Elgar, G., Foulger, R. E., Fowler, T., Furió-Tarí, P., Hackett, J. M., Halai, D., Hamblin, A., Henderson, S., Holman, J. E., Hubbard, T. J. P., Ibáñez, K., Jackson, R., Jones, L. J., Kasperaviciute, D., Kayikci, M., Lahnstein, L., Lawson, L., Leigh, S. E. A., and Leong, I. U. S.

Published
2020
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6. Improving interpretation of cardiac phenotypes and enhancing discovery with expanded knowledge in the gene ontology

Author

Lovering, R, Roncaglia, P, Howe, D, Laulederkind, S, Khodiyar, V, Berardini, T, Tweedie, S, Foulger, R, Osumi-Sutherland, D, Campbell, N, Huntley, R, Talmud, P, Blake, J, Breckenridge, R, Riley, P, Lambiase, P, Elliott, P, Clapp, L, Tinker, A, and Hill, D

Subjects
Proteomics, data curation, Heart Diseases, Computational Biology, Heart, Molecular Sequence Annotation, Original Articles, arrhythmias, cardiac, electrophysiology, Gene Ontology, Phenotype, Databases, Genetic, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Humans, genetics, transcriptome
Abstract

Supplemental Digital Content is available in the text., Background: A systems biology approach to cardiac physiology requires a comprehensive representation of how coordinated processes operate in the heart, as well as the ability to interpret relevant transcriptomic and proteomic experiments. The Gene Ontology (GO) Consortium provides structured, controlled vocabularies of biological terms that can be used to summarize and analyze functional knowledge for gene products. Methods and Results: In this study, we created a computational resource to facilitate genetic studies of cardiac physiology by integrating literature curation with attention to an improved and expanded ontological representation of heart processes in the Gene Ontology. As a result, the Gene Ontology now contains terms that comprehensively describe the roles of proteins in cardiac muscle cell action potential, electrical coupling, and the transmission of the electrical impulse from the sinoatrial node to the ventricles. Evaluating the effectiveness of this approach to inform data analysis demonstrated that Gene Ontology annotations, analyzed within an expanded ontological context of heart processes, can help to identify candidate genes associated with arrhythmic disease risk loci. Conclusions: We determined that a combination of curation and ontology development for heart-specific genes and processes supports the identification and downstream analysis of genes responsible for the spread of the cardiac action potential through the heart. Annotating these genes and processes in a structured format facilitates data analysis and supports effective retrieval of gene-centric information about cardiac defects.

Published
2018

8. A Misexpression Screen to Identify Novel Regulators of Growth and Proliferation in Drosophila

Author

Foulger, R. E., Goberdhan, D. C. I., and Wilson, C.

Subjects
Cell proliferation -- Genetic aspects, Drosophila -- Genetic aspects, Cells -- Growth, Developmental genetics -- Research, Biological sciences
Abstract

Cell proliferation and cell growth are tightly regulated during development in order to determine both organ size and the overall size of the organism. These processes are controlled both by environmental factors and also by hormones and growth receptors. Studies in Drosophila have highlighted an insulin receptor signaling pathway highly homologous to the mammalian cascade, that plays a unique in vivo role in regulating both cell size and number in tissues. We have performed a misexpression screen, pioneered by P. Rorth, to identify novel molecules that affect cell growth when overexpressed. In this preliminary strategy over 2000 EP lines, probably representing at least 1000 different genes, were expressed under the control of wing-specific and eye-specific GAL4 drivers, and the resulting flies were screened for effects on patterning and growth of these organs. Over 100 lines exhibited a putative growth phenotype in the eye and/or in the wing. In a secondary screen these selected strains were crossed to further eye-specific and wing-specific GAL4 drivers. We are currently focusing on three expression lines from this screen which affect organ and cell size in the eye and wing. In multiple assays one of these lines acts antagonistically to PTEN, a lipid phosphatase tumor suppressor acting downstream of the insulin receptor, consistent with a possible role in positively regulating insulin receptor signaling. The insertion that drives overexpression in this line does not lie within or close to any previously characterized Drosophila genes, although database searches place a number of ESTs nearby. A detailed molecular and genetic characterization of this line is currently in progress. Two other lines also regulate growth, but their effects are more tissue specific.

Published
2001

9. The Gene Ontology in 2010: extensions and refinements

Author

Berardini, Tz, Li, D, Huala, E, Bridges, S, Burgess, S, Mccarthy, F, Carbon, S, Lewis, Se, Mungall, Cj, Abdulla, A, Wood, V, Feltrin, E, Valle, Giorgio, Chisholm, Rl, Fey, P, Gaudet, P, Kibbe, W, Basu, S, Bushmanova, Y, Eilbeck, K, Siegele, Da, Mcintosh, B, Renfro, D, Zweifel, A, Hu, Jc, Ashburner, M, Tweedie, S, ALAM FARUQUE, Y, Apweiler, R, Auchinchloss, A, Bairoch, A, Barrell, D, Binns, D, Blatter, Mc, Bougueleret, L, Boutet, E, Breuza, L, Bridge, A, Browne, P, Chan, Wm, Coudert, E, Daugherty, L, Dimmer, E, Eberhardt, R, Estreicher, A, Famiglietti, L, FERRO ROJAS, S, Feuermann, M, Foulger, R, GRUAZ GUMOWSKI, N, Hinz, U, Huntley, R, Jimenez, S, Jungo, F, Keller, G, Laiho, K, Legge, D, Lemercier, P, Lieberherr, D, Magrane, M, O'Donovan, C, Pedruzzi, I, Poux, S, Rivoire, C, Roechert, B, Sawford, T, Schneider, M, Stanley, E, Stutz, A, Sundaram, S, Tognolli, M, Xenarios, I, Harris, Ma, Deegan, Ji, Ireland, A, Lomax, J, Jaiswal, P, Chibucos, M, Giglio, Mg, Wortman, J, Hannick, L, Madupu, R, Botstein, D, Dolinski, K, Livstone, Ms, Oughtred, R, Blake, Ja, Bult, C, Diehl, Ad, Dolan, M, Drabkin, H, Eppig, Jt, Hill, Dp, Ni, L, Ringwald, M, Sitnikov, D, Collmer, C, TORTO ALALIBO, T, Laulederkind, S, Shimoyama, M, Twigger, S, D'Eustachio, P, Matthews, L, Balakrishnan, R, Binkley, G, Cherry, Jm, Christie, Kr, Costanzo, Mc, Engel, Sr, Fisk, Dg, Hirschman, Je, Hitz, Bc, Hong, El, Krieger, Cj, Miyasato, Sr, Nash, Rs, Park, J, Skrzypek, Ms, Weng, S, Wong, Ed, Aslett, M, Chan, J, Kishore, R, Sternberg, P, VAN AUKE, K, Khodiyar, Vk, Lovering, Rc, Talmud, Pj, Howe, D, Westerfield, M., Gene Ontology Consortium, Berardini, TZ., Li, D., Huala, E., Bridges, S., Burgess, S., McCarthy, F., Carbon, S., Lewis, SE., Mungall, CJ., Abdulla, A., Wood, V., Feltrin, E., Valle, G., Chisholm, RL., Fey, P., Gaudet, P., Kibbe, W., Basu, S., Bushmanova, Y., Eilbeck, K., Siegele, DA., McIntosh, B., Renfro, D., Zweifel, A., Hu, JC., Ashburner, M., Tweedie, S., Alam-Faruque, Y., Apweiler, R., Auchinchloss, A., Bairoch, A., Barrell, D., Binns, D., Blatter, MC., Bougueleret, L., Boutet, E., Breuza, L., Bridge, A., Browne, P., Chan, WM., Coudert, E., Daugherty, L., Dimmer, E., Eberhardt, R., Estreicher, A., Famiglietti, L., Ferro-Rojas, S., Feuermann, M., Foulger, R., Gruaz-Gumowski, N., Hinz, U., Huntley, R., Jimenez, S., Jungo, F., Keller, G., Laiho, K., Legge, D., Lemercier, P., Lieberherr, D., Magrane, M., O'Donovan, C., Pedruzzi, I., Poux, S., Rivoire, C., Roechert, B., Sawford, T., Schneider, M., Stanley, E., Stutz, A., Sundaram, S., Tognolli, M., Xenarios, I., Harris, MA., Deegan, JI., Ireland, A., Lomax, J., Jaiswal, P., Chibucos, M., Giglio, MG., Wortman, J., Hannick, L., Madupu, R., Botstein, D., Dolinski, K., Livstone, MS., Oughtred, R., Blake, JA., Bult, C., Diehl, AD., Dolan, M., Drabkin, H., Eppig, JT., Hill, DP., Ni, L., Ringwald, M., Sitnikov, D., Collmer, C., Torto-Alalibo, T., Laulederkind, S., Shimoyama, M., Twigger, S., D'Eustachio, P., Matthews, L., Balakrishnan, R., Binkley, G., Cherry, JM., Christie, KR., Costanzo, MC., Engel, SR., Fisk, DG., Hirschman, JE., Hitz, BC., Hong, EL., Krieger, CJ., Miyasato, SR., Nash, RS., Park, J., Skrzypek, MS., Weng, S., Wong, ED., Aslett, M., Chan, J., Kishore, R., Sternberg, P., Van Auke, K., Khodiyar, VK., Lovering, RC., Talmud, PJ., Howe, D., and Westerfield, M.

Subjects
Information Storage and Retrieval, Ontology (information science), Biology, Bioinformatics, World Wide Web, Set (abstract data type), 03 medical and health sciences, Annotation, User-Computer Interface, 0302 clinical medicine, Controlled vocabulary, Databases, Genetic, Genetics, Animals, Humans, Databases, Protein, Computational Biology/methods, Computational Biology/trends, Databases, Nucleic Acid, Genomics, Information Storage and Retrieval/methods, Internet, Software, Vocabulary, Controlled, 030304 developmental biology, Structure (mathematical logic), 0303 health sciences, Gene ontology, business.industry, Computational Biology, Usability, Articles, ComputingMethodologies_GENERAL, business, 030217 neurology & neurosurgery
Abstract

The Gene Ontology (GO) Consortium (http://www.geneontology.org) (GOC) continues to develop, maintain and use a set of structured, controlled vocabularies for the annotation of genes, gene products and sequences. The GO ontologies are expanding both in content and in structure. Several new relationship types have been introduced and used, along with existing relationships, to create links between and within the GO domains. These improve the representation of biology, facilitate querying, and allow GO developers to systematically check for and correct inconsistencies within the GO. Gene product annotation using GO continues to increase both in the number of total annotations and in species coverage. GO tools, such as OBO-Edit, an ontology-editing tool, and AmiGO, the GOC ontology browser, have seen major improvements in functionality, speed and ease of use.

Published
2010

10. NeuroChip, an updated version of the NeuroX genotyping platform to rapidly screen for variants associated with neurological diseases

Author

Blauwendraat, C., Faghri, F., Pihlstrom, L., Geiger, J. T., Elbaz, A., Lesage, S., Corvol, J. -C., May, P., Nicolas, A., Abramzon, Y., Murphy, N. A., Gibbs, J. R., Ryten, M., Ferrari, R., Bras, J., Guerreiro, R., Williams, J., Sims, R., Lubbe, S., Hernandez, D. G., Mok, K. Y., Robak, L., Campbell, R. H., Rogaeva, E., Traynor, B. J., Chia, R., Chung, S. J., Hardy, J. A., Brice, A., Wood, N. W., Houlden, H., Shulman, J. M., Morris, H. R., Gasser, T., Kruger, R., Heutink, P., Sharma, M., Simon-Sanchez, J., Nalls, M. A., Singleton, A. B., Scholz, S. W., Noyce, A. J., Giri, A., Oehmig, A., Tucci, A., Schulte, C., Cookson, M. R., Kia, D., Danjou, F., Charlesworth, G., Plun-Favreau, H., Holmans, P., Jansen, I., Hardy, J., Bras, J. M., Quinn, J., Botia, J. A., Billingsley, K., R'Bibo, L., Lungu, C., Martinez, M., Escott-Price, V., Mencacci, N. E., Topley, Lewis, Denny, P., Rizzu, P., Taba, P., Lovering, R., Ogalla, R. D., Foulger, R., Finkbeiner, S., Sveinbjornsdottir, S., Scholz, S., Koks, S., Foltynie, T., Price, T. R., Sheerin, U. -M., Williams, N., Reed, X., Wang, L., Brockmann, K., Oertel, W., Klein, C., Mohamed, F., Malard, L., Corti, O., Drouet, V., Goldwurm, S., Tesei, S., Canesi, M., Valente, E. M., Petrucci, S., Ginevrino, M., Toft, M., Aasly, J., Henriksen, S. P., Saetehaug, C., Orr-Urtreger, A., Giladi, N., Ferreira, J., Guedes, L. C., Bouca-Machado, R., Coelho, M., Rosa, M. M., Tolosa, E., Fernandez-Santiago, R., Ezquerra, M., Marti, M. J., Glaab, E., Balling, R., and Chung, S. -J.

Subjects
0301 basic medicine, Aging, methods [Genome-Wide Association Study], 0302 clinical medicine, Corticobasal degeneration, neurodegenerative diseases, humans, risk, high-throughput screening assays, education.field_of_study, General Neuroscience, neurodegeneration, genetics [Genetic Variation], 3. Good health, Neurochip, alleles, methods [Genotyping Techniques], Frontotemporal dementia, Risk, Population, methods [High-Throughput Screening Assays], Computational biology, Genetic screening, genotyping, NeuroChip, NeuroX, apolipoproteins E, genetic variation, genome-wide association study, genotyping techniques, Article, Progressive supranuclear palsy, 03 medical and health sciences, Apolipoproteins E, medicine, Humans, Dementia, ddc:610, education, Genotyping, Alleles, business.industry, medicine.disease, 030104 developmental biology, genetics [Neurodegenerative Diseases], genetics [Apolipoproteins E], Neurology (clinical), Geriatrics and Gerontology, business, Neuroscience, 030217 neurology & neurosurgery, Imputation (genetics), Developmental Biology
Abstract

Genetics has proven to be a powerful approach in neurodegenerative diseases research, resulting in the identification of numerous causal and risk variants. Previously, we introduced the NeuroX Illumina genotyping array, a fast and efficient genotyping platform designed for the investigation of genetic variation in neurodegenerative diseases. Here, we present its updated version, named NeuroChip. The NeuroChip is a low-cost, custom-designed array containing a tagging variant backbone of about 306,670 variants complemented with a manually curated custom content comprised of 179,467 variants implicated in diverse neurological diseases, including Alzheimer's disease, Parkinson's disease, Lewy body dementia, amyotrophic lateral sclerosis, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy. The tagging backbone was chosen because of the low cost and good genome-wide resolution; the custom content can be combined with other backbones, like population or drug development arrays. Using the NeuroChip, we can accurately identify rare variants and impute over 5.3 million common SNPs from the latest release of the Haplotype Reference Consortium. In summary, we describe the design and usage of the NeuroChip array and show its capability for detecting rare pathogenic variants in numerous neurodegenerative diseases. The NeuroChip has a more comprehensive and improved content, which makes it a reliable, high-throughput, cost-effective screening tool for genetic research and molecular diagnostics in neurodegenerative diseases.

Published
2017
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13. Drosophila SnoN modulates growth and patterning by antagonizing TGF-beta signalling

Author

Ramel, M.C., Emery, C.S., Foulger, R., Goberdhan, Deborah C.I., van den Heuvel, M., Wilson, Clive, Ramel, M.C., Emery, C.S., Foulger, R., Goberdhan, Deborah C.I., van den Heuvel, M., and Wilson, Clive

Abstract

Signalling by TGF-beta ligands through the Smad family of transcription factors is critical for developmental patterning and growth. Disruption of this pathway has been observed in various cancers. In vertebrates, members of the Ski/Sno protein family can act as negative regulators of TGF-beta signalling, interfering with the Smad machinery to inhibit the transcriptional output of this pathway. In some contexts ski/sno genes function as tumour suppressors, but they were originally identified as oncogenes, whose expression is up-regulated in many tumours. These growth regulatory effects and the normal physiological functions of Ski/Sno proteins have been proposed to result from changes in TGF-beta signalling. However, this model is controversial and may be over-simplified, because recent findings indicate that Ski/Sno proteins can affect other signalling pathways. To address this issue in an in vivo context, we have analyzed the function of the Drosophila Ski/Sno orthologue, SnoN. We found that SnoN inhibits growth when overexpressed, indicating a tumour suppressor role in flies. It can act in multiple tissues to selectively and cell autonomously antagonise signalling by TGF-beta ligands from both the BMP and Activin sub-families. By contrast, analysis of a snoN mutant indicates that the gene does not play a global role in TGF-beta-mediated functions, but specifically inhibits TGF-beta-induced wing vein formation. We propose that SnoN normally functions redundantly with other TGF-beta pathway antagonists to finely adjust signalling levels, but that it can behave as an extremely potent inhibitor of TGF-beta signalling when highly expressed, highlighting the significance of its deregulation in cancer cells.

Published
2007

18. Corrigendum: Opportunities and Challenges for Molecular Understanding of Ciliopathies–The 100,000 Genomes Project.

Author

Wheway, Gabrielle, Mitchison, Hannah M., Ambrose, J. C., Baple, E. L., Bleda, M., Boardman-Pretty, F., Boissiere, J. M., Boustred, C. R., Caulfield, M. J., Chan, G. C., Craig, C. E. H., Daugherty, L. C., de, Burca A., Devereau, A., Elgar, G., Foulger, R. E., Fowler, T., Furió-Tarí, P., Hackett, J. M., and Halai, D.

Subjects
GENOMES, MEDICAL care, STREET children
Abstract

Highlights from the article: Suitable gene panels with features overlapping the phenotype e.g., retinal dystrophy gene panel, Protein altering variants affecting genes not in the virtual gene 100,000 Genomes Project uses data provided by patients and Copyright of Frontiers in Genetics is the property of Frontiers Media S.A. and its content may.

Published
2019
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19. Control Measures

Author

Foulger R

Subjects
Text mining, Computer science, business.industry, Control (management), Public Health, Environmental and Occupational Health, business, Data science
Published
1980
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20. Influence of composition and microstructure on mechanical working properties of copper-base alloys

Author

Foulger, R. V. and Nicholls, E.

Abstract

Alloy compositions for optimum hot and cold mechanical working operations are reviewed with special reference to brasses, bronzes, and nickel silvers. The effects of impurities are discussed, with the compilation of realistic specifications. The control of microstructure and grain size and their relevance to subsequent operations such as deep drawing are examined. The influence of structure and composition on inherent weaknesses such as ‘season cracking’, ‘fire cracking’, and ‘stretcher strain’ marking are considered, together with special effects such as ‘microduplexing’ and ‘stress relieving’ to achieve enhanced spring properties.

Published
1976
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21. The Gene Ontology (GO) database and informatics resource

Author

Ma, Harris, Clark J, Ireland A, Lomax J, Ashburner M, Foulger R, Eilbeck K, Lewis S, Marshall B, Mungall C, Richter J, Gm, Rubin, Ja, Blake, Bult C, Dolan M, Drabkin H, Jt, Eppig, Dp, Hill, Ni L, Ringwald M, Balakrishnan R, Jm, Cherry, Kr, Christie, Mc, Costanzo, Ss, Dwight, Engel S, Dg, Fisk, Je, Hirschman, El, Hong, Rs, Nash, Sethuraman A, Cl, Theesfeld, Botstein D, Dolinski K, Feierbach B, Berardini T, Mundodi S, Sy, Rhee, Rolf Apweiler, Barrell D, Camon E, Dimmer E, Lee V, Chisholm R, Gaudet P, Kibbe W, Kishore R, Em, Schwarz, Sternberg P, Gwinn M, Hannick L, Wortman J, Berriman M, Wood V, de la Cruz N, Tonellato P, Jaiswal P, Seigfried T, White R, and Gene Ontology Consortium

23. Food Hygiene

Author

Foulger, R.

Subjects
LEGISLATION, SANITATION, ENVIRONMENTAL health
Published
1980

24. The Gene Ontology: enhancements for 2011

Author

P D'Eustachio, Benjamin C. Hitz, Julie Park, Paul Browne, Douglas G. Howe, Cynthia J. Krieger, Kalpana Karra, Stan Laulederkind, Karen R. Christie, Susan Tweedie, Eurie L. Hong, Lydie Bougueleret, Michele Magrane, Cathy R. Gresham, Rolf Apweiler, Lisa Matthews, Dong Li, Philippa J. Talmud, Ioannis Xenarios, J. M. Cherry, Tanya Z. Berardini, Deborah A. Siegele, Rama Balakrishnan, D. Sitnikov, A. Auchinchloss, Selina S. Dwight, Tony Sawford, Paul J. Kersey, Ruth C. Lovering, Ruth Y. Eberhardt, Ursula Hinz, Lakshmi Pillai, Sylvain Poux, Edith D. Wong, Klemens Pichler, Kati Laiho, Malcolm J. Gardner, Stephen G. Oliver, Lionel Breuza, Kara Dolinski, P Lemercier, Kristian B. Axelsen, Midori A. Harris, Adrienne E. Zweifel, H. Drabkin, Guillaume Keller, Marek S. Skrzypek, Daniel M. Staines, Fiona M. McCarthy, Nicholas H. Brown, Mark D. McDowall, Antonia Lock, Mary Shimoyama, Maria C. Costanzo, Teresia Buza, S. Jimenez, Rex L. Chisholm, Paul W. Sternberg, Hui Wang, Nadine Gruaz-Gumowski, Chantal Hulo, Rebecca E. Foulger, Melinda R. Dwinell, Judith A. Blake, Marcus C. Chibucos, B. K. McIntosh, C. D. Amundsen, Jane Lomax, L Famiglietti, Tom Hayman, Michael Tognolli, Eva Huala, James C. Hu, Patrick Masson, Maria Jesus Martin, Benoit Bely, Shuai Weng, Heather C. Wick, E. Dimmer, L. Ni, Catherine Rivoire, Christopher J. Mungall, H. Sehra, P. Duek-Roggli, Maria Victoria Schneider, Dianna G. Fisk, Michael S. Livstone, Ivo Pedruzzi, Shyamala Sundaram, Donna K. Slonim, Isabelle Cusin, Stuart R. Miyasato, Timothy F. Lowry, Varsha K. Khodiyar, Seth Carbon, Elisabeth Coudert, Jürg Bähler, Juancarlos Chan, Evelyn Camon, Daniel P. Renfro, Anne Estreicher, M. C. Blatter, Robert S. Nash, P Gaudet, Sven Heinicke, K. Van Auken, Stacia R. Engel, Alan Bridge, Ralf Stephan, Mary E. Dolan, Shane C. Burgess, Petra Fey, Shur-Jen Wang, Damien Lieberherr, Duncan Legge, P. Porras Millán, Andre Stutz, Yasmin Alam-Faruque, Gail Binkley, Bernd Roechert, S. Branconi-Quintaje, Ghislaine Argoud-Puy, S. Basu, Kim Rutherford, M. Moinat, Monte Westerfield, Arnaud Gos, Eleanor J Stanley, Valerie Wood, Ranjana Kishore, Diego Poggioli, S. Ferro-Rojas, Victoria Petri, Florence Jungo, Suzanna E. Lewis, Emmanuel Boutet, Warren A. Kibbe, M Feuermann, Claire O'Donovan, W. M. Chan, J. James, David P. Hill, Rachael P. Huntley, M. Gwinn Giglio, Paul Thomas, Jodi E. Hirschman, Paola Roncaglia, Gene Ontology Consortium, Blake, JA., Dolan, M., Drabkin, H., Hill, DP., Ni, L., Sitnikov, D., Burgess, S., Buza, T., Gresham, C., McCarthy, F., Pillai, L., Wang, H., Carbon, S., Lewis, SE., Mungall, CJ., Gaudet, P., Chisholm, RL., Fey, P., Kibbe, WA., Basu, S., Siegele, DA., McIntosh, BK., Renfro, DP., Zweifel, AE., Hu, JC., Brown, NH., Tweedie, S., Alam-Faruque, Y., Apweiler, R., Auchinchloss, A., Axelsen, K., Argoud-Puy, G., Bely, B., Blatter, M-., Bougueleret, L., Boutet, E., Branconi, S., Breuza, L., Bridge, A., Browne, P., Chan, WM., Coudert, E., Cusin, I., Dimmer, E., Duek-Roggli, P., Eberhardt, R., Estreicher, A., Famiglietti, L., Ferro-Rojas, S., Feuermann, M., Gardner, M., Gos, A., Gruaz-Gumowski, N., Hinz, U., Hulo, C., Huntley, R., James, J., Jimenez, S., Jungo, F., Keller, G., Laiho, K., Legge, D., Lemercier, P., Lieberherr, D., Magrane, M., Martin, MJ., Masson, P., Moinat, M., O'Donovan, C., Pedruzzi, I., Pichler, K., Poggioli, D., Porras Millán, P., Poux, S., Rivoire, C., Roechert, B., Sawford, T., Schneider, M., Sehra, H., Stanley, E., Stutz, A., Sundaram, S., Tognolli, M., Xenarios, I., Foulger, R., Lomax, J., Roncaglia, P., Camon, E., Khodiyar, VK., Lovering, RC., Talmud, PJ., Chibucos, M., Gwinn Giglio, M., Dolinski, K., Heinicke, S., Livstone, MS., Stephan, R., Harris, MA., Oliver, SG., Rutherford, K., Wood, V., Bahler, J., Lock, A., Kersey, PJ., McDowall, MD., Staines, DM., Dwinell, M., Shimoyama, M., Laulederkind, S., Hayman, T., Wang, S-., Petri, V., Lowry, T., D'Eustachio, P., Matthews, L., Amundsen, CD., Balakrishnan, R., Binkley, G., Cherry, JM., Christie, KR., Costanzo, MC., Dwight, SS., Engel, SR., Fisk, DG., Hirschman, JE., Hitz, BC., Hong, EL., Karra, K., Krieger, CJ., Miyasato, SR., Nash, RS., Park, J., Skrzypek, MS., Weng, S., Wong, ED., Berardini, TZ., Li, D., Huala, E., Slonim, D., Wick, H., Thomas, P., Chan, J., Kishore, R., Sternberg, P., Van Auken, K., Howe, D., and Westerfield, M.

Subjects
Quality Control, 0303 health sciences, media_common.quotation_subject, Databases, Genetic, Molecular Sequence Annotation/standards, Vocabulary, Controlled, Inference, Molecular Sequence Annotation, Articles, Biology, Ontology (information science), World Wide Web, Open Biomedical Ontologies, 03 medical and health sciences, Annotation, 0302 clinical medicine, Resource (project management), Controlled vocabulary, Genetics, Social media, Function (engineering), 030217 neurology & neurosurgery, 030304 developmental biology, media_common
Abstract

The Gene Ontology (GO) (http://www.geneontology.org) is a community bioinformatics resource that represents gene product function through the use of structured, controlled vocabularies. The number of GO annotations of gene products has increased due to curation efforts among GO Consortium (GOC) groups, including focused literature-based annotation and ortholog-based functional inference. The GO ontologies continue to expand and improve as a result of targeted ontology development, including the introduction of computable logical definitions and development of new tools for the streamlined addition of terms to the ontology. The GOC continues to support its user community through the use of e-mail lists, social media and web-based resources.

Published
2011
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25. The Universal Protein Resource (UniProt) in 2010

Author

Elisabeth Gasteiger, Amos Bairoch, John Garavelli, Julius Jacobsen, Lionel Breuza, Rachael Huntley, Rolf Apweiler, Christian J. A. SIGRIST, Rebecca Foulger, Jerven Bolleman, Raja Mazumder, Ivo Pedruzzi, Florence Jungo, Anaïs Mottaz, Michael Tognolli, Emmanuel Boutet, Claire O'Donovan, Edward Turner, Sandra Orchard, Patrick Masson, Peter McGarvey, Nicole Redaschi, Sébastien Géhant, Michele Magrane, Anne Estreicher, Alan Bridge, Michel Schneider, Daniel Barrell, Benoit Bely, Anne Morgat, Sylvain Poux, Petra Langendijk-Genevaux, Maria-Jesus Martin, Catherine Rivoire, Elisabeth Coudert, Rasko Leinonen, Cecilia Arighi, UniProt Consortium, Apweiler, R., Martin, MJ., O'Donovan, C., Magrane, M., Alam-Faruque, Y., Antunes, R., Barrell, D., Bely, B., Bingley, M., Binns, D., Bower, L., Browne, P., Chan, WM., Dimmer, E., Eberhardt, R., Fedotov, A., Foulger, R., Garavelli, J., Huntley, R., Jacobsen, J., Kleen, M., Laiho, K., Leinonen, R., Legge, D., Lin, Q., Liu, W., Luo, J., Orchard, S., Patient, S., Poggioli, D., Pruess, M., Corbett, M., di Martino, G., Donnelly, M., van Rensburg, P., Bairoch, A., Bougueleret, L., Xenarios, I., Altairac, S., Auchincloss, A., Argoud-Puy, G., Axelsen, K., Baratin, D., Blatter, MC., Boeckmann, B., Bolleman, J., Bollondi, L., Boutet, E., Quintaje, SB., Breuza, L., Bridge, A., deCastro, E., Ciapina, L., Coral, D., Coudert, E., Cusin, I., Delbard, G., Doche, M., Dornevil, D., Roggli, PD., Duvaud, S., Estreicher, A., Famiglietti, L., Feuermann, M., Gehant, S., Farriol-Mathis, N., Ferro, S., Gasteiger, E., Gateau, A., Gerritsen, V., Gos, A., Gruaz-Gumowski, N., Hinz, U., Hulo, C., Hulo, N., James, J., Jimenez, S., Jungo, F., Kappler, T., Keller, G., Lachaize, C., Lane-Guermonprez, L., Langendijk-Genevaux, P., Lara, V., Lemercier, P., Lieberherr, D., de Oliveira Lima, T., Mangold, V., Martin, X., Masson, P., Moinat, M., Morgat, A., Mottaz, A., Paesano, S., Pedruzzi, I., Pilbout, S., Pillet, V., Poux, S., Pozzato, M., Redaschi, N., Rivoire, C., Roechert, B., Schneider, M., Sigrist, C., Sonesson, K., Staehli, S., Stanley, E., Stutz, A., Sundaram, S., Tognolli, M., Verbregue, L., Veuthey, AL., Yip, L., Zuletta, L., Wu, C., Arighi, C., Arminski, L., Barker, W., Chen, C., Chen, Y., Hu, ZZ., Huang, H., Mazumder, R., McGarvey, P., Natale, DA., Nchoutmboube, J., Petrova, N., Subramanian, N., Suzek, BE., Ugochukwu, U., Vasudevan, S., Vinayaka, CR., Yeh, LS., and Zhang, J.

Subjects
Proteomics, Internet, 0303 health sciences, Proteome, 030302 biochemistry & molecular biology, Computational Biology, Information Storage and Retrieval, Genome, Viral, Articles, Europe, 03 medical and health sciences, Algorithms, Animals, Computational Biology/methods, Computational Biology/trends, Databases, Nucleic Acid, Databases, Protein, Genome, Fungal, Humans, Information Storage and Retrieval/methods, Protein Isoforms, Software, Genetics, 030304 developmental biology
Abstract

The primary mission of UniProt is to support biological research by maintaining a stable, comprehensive, fully classified, richly and accurately annotated protein sequence knowledgebase, with extensive cross-references and querying interfaces freely accessible to the scientific community. UniProt is produced by the UniProt Consortium which consists of groups from the European Bioinformatics Institute (EBI), the Swiss Institute of Bioinformatics (SIB) and the Protein Information Resource (PIR). UniProt is comprised of four major components, each optimized for different uses: the UniProt Archive, the UniProt Knowledgebase, the UniProt Reference Clusters and the UniProt Metagenomic and Environmental Sequence Database. UniProt is updated and distributed every 3 weeks and can be accessed online for searches or download at http://www.uniprot.org.

Published
2009
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26. Ongoing and future developments at the Universal Protein Resource

Author

Vicente Lara, Arnaud Gos, Nikolas Pontikos, L. Bollondi, L Famiglietti, Barker Wc, Chuming Chen, Michael Tognolli, Patrick Masson, Salvo Paesano, Tony Sawford, Sandrine Pilbout, Jerven Bolleman, Jian Zhang, S Staehli, Elisabeth Gasteiger, David Binns, Ursula Hinz, Nadine Gruaz-Gumowski, Chantal Hulo, Maria Jesus Martin, M. Corbett, Veuthey Al, Paul Browne, Guillaume Keller, S. Jimenez, Roberts Nv, Brigitte Boeckmann, Natale Da, Suzek Be, Edward Turner, T. Kappler, Steven Rosanoff, Leslie Arminski, Florence Jungo, M Donnelly, P. Dubey, Ruth Y. Eberhardt, Lydie Bougueleret, Vivienne Baillie Gerritsen, Maria Victoria Schneider, Lionel Breuza, Isabelle Cusin, Delphine Baratin, E. Dimmer, Rachael P. Huntley, Julius O.B. Jacobsen, Arighi Cn, Quintaje Sb, Alan Bridge, Nicole Redaschi, Shyamala Sundaram, Peter B. McGarvey, Rebecca E. Foulger, Duncan Legge, Andre Stutz, Monica Pozzato, Raja Mazumder, Anne Morgat, M Doche, K Sonesson, Anne Estreicher, Blatter Mc, Manuela Pruess, Serenella Ferro, Séverine Duvaud, F. Fazzini, Rolf Apweiler, Natarajan Tg, E. Stanley, M Feuermann, Claire O'Donovan, J. James, Ivo Pedruzzi, Castro Lg, Wu Ch, M Bingley, W Liu, He Huang, Bernd Roechert, Laure Verbregue, Elisabeth Coudert, Ioannis Xenarios, M. Moinat, Sandra Orchard, P Lemercier, Damien Lieberherr, Ricardo Antunes, Ghislaine Argoud-Puy, Sebastien Gehant, Qiang Wang, Klemens Pichler, S. Patient, Nicolas Hulo, Diego Poggioli, J. Nchoutmboube, Emmanuel Boutet, H. Sehra, Chan Wm, Yasmin Alam-Faruque, M. Kleen, Van Rensburg P, Kati Laiho, Kristian B. Axelsen, John S. Garavelli, Christian J. A. Sigrist, Amos Marc Bairoch, Yongxing Chen, A. Fedotov, Yeh Ls, Sylvain Poux, Lynette Bower, Quan Lin, Daniel Barrell, Benoit Bely, U. Ugochukwu, Xavier D. Martin, Catherine Rivoire, E. Decastro, Jie Luo, Alain Gateau, Michele Magrane, Dolnide Dornevil, Vinayaka Cr, Andrea H. Auchincloss, Yuqi Wang, An algorithmic view on genomes, cells, and environments (BAMBOO), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL), Institut de Microélectronique, Electromagnétisme et Photonique - Laboratoire d'Hyperfréquences et Caractérisation (IMEP-LAHC), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Institut de minéralogie et de physique des milieux condensés (IMPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Institut de Physique du Globe de Paris (IPG Paris)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria), Université de Lausanne (UNIL), Université Pierre et Marie Curie - Paris 6 (UPMC)-IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), UniProt Consortium, Apweiler, R., Martin, MJ., O'Donovan, C., Magrane, M., Alam-Faruque, Y., Antunes, R., Barrell, D., Bely, B., Bingley, M., Binns, D., Bower, L., Browne, P., Chan, WM., Dimmer, E., Eberhardt, R., Fazzini, F., Fedotov, A., Foulger, R., Garavelli, J., Castro, LG., Huntley, R., Jacobsen, J., Kleen, M., Laiho, K., Legge, D., Lin, Q., Liu, W., Luo, J., Orchard, S., Patient, S., Pichler, K., Poggioli, D., Pontikos, N., Pruess, M., Rosanoff, S., Sawford, T., Sehra, H., Turner, E., Corbett, M., Donnelly, M., van Rensburg, P., Xenarios, I., Bougueleret, L., Auchincloss, A., Argoud-Puy, G., Axelsen, K., Bairoch, A., Baratin, D., Blatter, MC., Boeckmann, B., Bolleman, J., Bollondi, L., Boutet, E., Quintaje, SB., Breuza, L., Bridge, A., deCastro, E., Coudert, E., Cusin, I., Doche, M., Dornevil, D., Duvaud, S., Estreicher, A., Famiglietti, L., Feuermann, M., Gehant, S., Ferro, S., Gasteiger, E., Gateau, A., Gerritsen, V., Gos, A., Gruaz-Gumowski, N., Hinz, U., Hulo, C., Hulo, N., James, J., Jimenez, S., Jungo, F., Kappler, T., Keller, G., Lara, V., Lemercier, P., Lieberherr, D., Martin, X., Masson, P., Moinat, M., Morgat, A., Paesano, S., Pedruzzi, I., Pilbout, S., Poux, S., Pozzato, M., Redaschi, N., Rivoire, C., Roechert, B., Schneider, M., Sigrist, C., Sonesson, K., Staehli, S., Stanley, E., Stutz, A., Sundaram, S., Tognolli, M., Verbregue, L., Veuthey, AL., Wu, CH., Arighi, CN., Arminski, L., Barker, WC., Chen, C., Chen, Y., Dubey, P., Huang, H., Mazumder, R., McGarvey, P., Natale, DA., Natarajan, TG., Nchoutmboube, J., Roberts, NV., Suzek, BE., Ugochukwu, U., Vinayaka, CR., Wang, Q., Wang, Y., Yeh, LS., and Zhang, J.

Subjects
Proteomics, 0303 health sciences, Sequence database, 030302 biochemistry & molecular biology, Proteins, Articles, Computational biology, Biology, Bioinformatics, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Systems Integration, Universal Protein Resource, 03 medical and health sciences, Information resource, Protein sequencing, Sequence Analysis, Protein, Metagenomics, UniProt Knowledgebase, Genetics, Databases, Protein/trends, Proteins/chemistry, Proteins/genetics, UniProt, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Databases, Protein, 030304 developmental biology
Abstract

International audience; The primary mission of Universal Protein Resource (UniProt) is to support biological research by maintaining a stable, comprehensive, fully classified, richly and accurately annotated protein sequence knowledgebase, with extensive cross-references and querying interfaces freely accessible to the scientific community. UniProt is produced by the UniProt Consortium which consists of groups from the European Bioinformatics Institute (EBI), the Swiss Institute of Bioinformatics (SIB) and the Protein Information Resource (PIR). UniProt is comprised of four major components, each optimized for different uses: the UniProt Archive, the UniProt Knowledgebase, the UniProt Reference Clusters and the UniProt Metagenomic and Environmental Sequence Database. UniProt is updated and distributed every 4 weeks and can be accessed online for searches or download at http://www.uniprot.org.

Published
2011
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27. From protein sequences to 3D-structures and beyond: the example of the UniProt knowledgebase

Author

Elisabeth Gasteiger, Amos Bairoch, John Garavelli, Julius Jacobsen, Lionel Breuza, Rachael Huntley, Rolf Apweiler, Christian J. A. SIGRIST, Rebecca Foulger, Raja Mazumder, Ivo Pedruzzi, Florence Jungo, Anaïs Mottaz, Michael Tognolli, Emmanuel Boutet, Claire O'Donovan, Edward Turner, Sandra Orchard, Patrick Masson, Peter McGarvey, Nicole Redaschi, Sébastien Géhant, Michele Magrane, Anne Estreicher, Alan Bridge, Daniel Barrell, Benoit Bely, Anne Morgat, Sylvain Poux, Petra Langendijk-Genevaux, Maria-Jesus Martin, Catherine Rivoire, Elisabeth Coudert, Rasko Leinonen, Cecilia Arighi, UniProt Consortium, Apweiler, R., Martin, MJ., O'Donovan, C., Magrane, M., Alam-Faruque, Y., Antunes, R., Barrell, D., Bely, B., Bingley, M., Binns, D., Bower, L., Browne, P., Chan, WM., Dimmer, E., Eberhardt, R., Fedotov, A., Foulger, R., Garavelli, J., Huntley, R., Jacobsen, J., Kleen, M., Laiho, K., Leinonen, R., Legge, D., Lin, Q., Liu, W., Luo, J., Orchard, S., Patient, S., Poggioli, D., Pruess, M., Corbett, M., di Martino, G., Donnelly, M., van Rensburg, P., Bairoch, A., Bougueleret, L., Xenarios, I., Altairac, S., Auchincloss, A., Argoud-Puy, G., Axelsen, K., Baratin, D., Blatter, MC., Boeckmann, B., Bolleman, J., Bollondi, L., Boutet, E., Quintaje, SB., Breuza, L., Bridge, A., de Castro, E., Ciapina, L., Coral, D., Coudert, E., Cusin, I., David, F., Delbard, G., Doche, M., Dornevil, D., Roggli, PD., Duvaud, S., Estreicher, A., Famiglietti, L., Feuermann, M., Gehant, S., Farriol-Mathis, N., Ferro, S., Gasteiger, E., Gateau, A., Gerritsen, V., Gos, A., Gruaz-Gumowski, N., Hinz, U., Hulo, C., Hulo, N., James, J., Jimenez, S., Jungo, F., Kappler, T., Keller, G., Lachaize, C., Lane-Guermonprez, L., Langendijk-Genevaux, P., Lara, V., Lemercier, P., Lieberherr, D., Lima Tde, O., Mangold, V., Martin, X., Masson, P., Moinat, M., Morgat, A., Mottaz, A., Paesano, S., Pedruzzi, I., Pilbout, S., Pillet, V., Poux, S., Pozzato, M., Redaschi, N., Rivoire, C., Roechert, B., Schneider, M., Sigrist, C., Sonesson, K., Staehli, S., Stanley, E., Stutz, A., Sundaram, S., Tognolli, M., Verbregue, L., Veuthey, AL., Yip, L., Zuletta, L., Wu, C., Arighi, C., Arminski, L., Barker, W., Chen, C., Chen, Y., Hu, ZZ., Huang, H., Mazumder, R., McGarvey, P., Natale, DA., Nchoutmboube, J., Petrova, N., Subramanian, N., Suzek, BE., Ugochukwu, U., Vasudevan, S., Vinayaka, CR., Yeh, LS., and Zhang, J.

Subjects
Proteomics, Binding Sites, Catalytic Domain, Databases, Protein, Knowledge Bases, Protein Conformation, Proteins/chemistry, Proteins/genetics, Sequence Analysis, Protein, Sequence analysis, Computer science, Annotation, Structural genomics, Context (language use), Review, Computational biology, Bioinformatics, 03 medical and health sciences, Cellular and Molecular Neuroscience, Protein 3D-structure, Swiss-Prot, Molecular Biology, UniProtKB, 030304 developmental biology, Pharmacology, 0303 health sciences, 030302 biochemistry & molecular biology, Proteins, Experimental data, Data flood, Cell Biology, Knowledgebase, Data access, Molecular Medicine, UniProt
Abstract

With the dramatic increase in the volume of experimental results in every domain of life sciences, assembling pertinent data and combining information from different fields has become a challenge. Information is dispersed over numerous specialized databases and is presented in many different formats. Rapid access to experiment-based information about well-characterized proteins helps predict the function of uncharacterized proteins identified by large-scale sequencing. In this context, universal knowledgebases play essential roles in providing access to data from complementary types of experiments and serving as hubs with cross-references to many specialized databases. This review outlines how the value of experimental data is optimized by combining high-quality protein sequences with complementary experimental results, including information derived from protein 3D-structures, using as an example the UniProt knowledgebase (UniProtKB) and the tools and links provided on its website ( http://www.uniprot.org/ ). It also evokes precautions that are necessary for successful predictions and extrapolations.

Published
2010

28. Advanced Practice Nurse-Led Research: Challenges and Approaches to Digital Health Programs' Evaluation Using Big Data.

Author

Klein CJ, Cooling M, Dalstrom M, Foulger R, Handler JA, and Bond WF

Subjects
Humans, United States, Medicaid, Digital Health, Advanced Practice Nursing, Big Data
Abstract

Advanced practice nurse leaders are in key positions within health systems to provide time and resources for implementation and evaluation of digital health services. As virtual monitoring programs become more embedded within nursing, nurse leaders and educators need to ensure that nurses are prepared to work within interprofessional teams to administer and evaluate them. This article discusses challenges and implementation strategy considerations for data curation and analysis using large datasets from the Medicaid population for research., Competing Interests: J.A.H. is chief executive officer and a shareholder in Keylog Solutions LLC; has received funding from Pfizer; is a shareholder in other healthcare companies including Whispersom Corporation, EmOpti LLC, HealthLab LLC, and Baxter Healthcare; serves in an advisory role to Whispersom Corporation, EmOpti LLC, and HealthLab LLC; and has various patents that have been granted or are pending. The remaining authors declare no conflicts of interest. The OSF Medicaid Innovation Collaborative (MIC) digital health programs are supported in part by the Illinois Department of Healthcare and Family Services as part of the Department's Healthcare Transformation Collaborative Program, USA (grant number not applicable). The MIC research study is supported by the OSF HealthCare Foundation, Peoria, Illinois. Funding supports only qualitative interviews (not described here) (grant number not applicable)., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Published
2024
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29. Screening for Social Determinants of Health: Active and Passive Information Retrieval Methods.

Author

Stewart de Ramirez S, Shallat J, McClure K, Foulger R, and Barenblat L

Subjects
Humans, Retrospective Studies, Housing, Information Storage and Retrieval, Social Determinants of Health, Mass Screening methods
Abstract

Screening for social determinants of health (SDOH) is recommended, but numerous barriers exist to implementing SDOH screening in clinical spaces. In this study, the authors identified how both active and passive information retrieval methods may be used in clinical spaces to screen for SDOH and meet patient needs. The authors conducted a retrospective sequential cohort analysis comparing the active identification of SDOH through a patient-led digital manual screening process completed in primary care offices from September 2019 to January 2020 and passive identification of SDOH through natural language processing (NLP) from September 2016 to August 2018, among 1735 patients at a large midwestern tertiary referral hospital system and its associated outlying primary care and outpatient facilities. The percent of patients identified by both the passive and active identification methods as experiencing SDOH varied from 0.3% to 4.7%. The active identification method identified social integration, domestic safety, financial resources, food insecurity, transportation, housing, and stress in proportions ranging from 5% to 36%. The passive method contributed to the identification of financial resource issues and stress, identifying 9.6% and 3% of patients to be experiencing these issues, respectively. SDOH documentation varied by provider type. The combination of passive and active SDOH screening methods can provide a more comprehensive picture by leveraging historic patient interactions, while also eliciting current patient needs. Using passive, NLP-based methods to screen for SDOH will also help providers overcome barriers that have historically prevented screening.

Published
2022
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30. Closing the Gap: A Comparison of Engagement Interventions to Achieve Equitable Breast Cancer Screening in Rural Illinois.

Author

Stewart de Ramirez S, McGarvey J, Lotz A, McGee M, Oderwald T, Floess K, Foulger R, Cooling M, and Handler JA

Subjects
Female, Humans, Mammography, Mass Screening, Medicaid, United States, Breast Neoplasms diagnosis, Breast Neoplasms prevention & control, Early Detection of Cancer
Abstract

Mammography screening rates are typically lower in those with less economic advantage (EA). This study, conducted at an integrated health care system covering a mixed rurality population, assessed the ability of interventions (text messages linking to a Web microsite, digital health care workers, and a community health fair) to affect mammography screening rates and disparity in those rates among different EA populations. Payor type served as a proxy for greater (commercially insured) versus lower (Medicaid insured) EA. 4,342 subjects were included across the preintervention ("Pre") and postintervention ("Post") periods. Interventions were prospectively applied to all Medicaid subjects and randomly selected commercial subjects. Applying interventions only to lower EA subjects reversed the screening rate disparity (2.6% Pre vs. -3.7% Post, odds ratio [OR] 2.4 P  < 0.01). When intervention arms ("Least," "More," "Most") were equally applied, screening rates in both EA groups significantly increased in the More arm (Medicaid OR = 2.04 P  = 0.04, Commercial OR = 3.08 P  < 0.01) and Most arm (Medicaid OR 2.57 P  < 0.01, Commercial OR 2.33 P  < 0.01), but not in the Least (text-only) arm (Medicaid OR 1.83 P  = 0.11, Commercial OR 1.72 P  = 0.09), although this text-only arm was inadequately powered to detect a difference. In summary, targeting interventions to those with lower EA reversed screening rate disparities, text messaging combined with other interventions improved screening rates in both groups, and future research is needed to determine whether interventions can simultaneously improve screening rates for all without worsening the disparity.

Published
2022
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31. Medicaid expansion and accessibility to healthcare: The Illinois experience.

Author

Dalstrom M, Weinzimmer LG, Foulger R, and Klein CJ

Subjects
Adult, Cross-Sectional Studies, Health Services Accessibility, Humans, Illinois, Patient Protection and Affordable Care Act, United States, Insurance Coverage, Medicaid
Abstract

Objective: The study examined the impact that the Medicaid expansion in Illinois had upon insurance rates, access to medical care, dental care, pharmaceuticals, and mental-health counseling between rural and urban counties., Design and Sample: A serial cross-sectional design was used to assess the health perceptions of adults living in Illinois., Measures: Survey data were collected in 2012 (n = 6,149) before the Medicaid expansion in Illinois and in 2015 (n = 3,532) after the expansion from rural (n = 4) and urban counties (n = 4)., Intervention: Medicaid expansion reduced the uninsured rate in both rural (16.39%-4.87%) and urban counties (17.05%-5.2%) and improved self-reported health. It also increased access to all types of healthcare, with the biggest increase in dental coverage., Results: Path analysis indicated that the Medicaid expansion β = -1.03 (p < .01) and poor versus not poor β = -1.50 (p < .01) were a significant predictor to no healthcare access. Rural verses urban location was not significant (β = 0.04); however, race/ethnicity was significantly different (p < .01)., Conclusion: Findings suggest that although the expansion has increased access to care overall, those who are the most vulnerable are still not benefiting equally from the expansion. Therefore, strategies to assist high-risk adults in enrolling and using their Medicaid coverage need to developed and implemented., (© 2021 Wiley Periodicals Inc.)

Published
2021
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32. The ins and outs of eukaryotic viruses: Knowledge base and ontology of a viral infection.

Author

Hulo C, Masson P, de Castro E, Auchincloss AH, Foulger R, Poux S, Lomax J, Bougueleret L, Xenarios I, and Le Mercier P

Subjects
Databases, Genetic, Virus Replication, Viruses genetics, Viruses pathogenicity, Eukaryotic Cells virology, Terminology as Topic, Virus Diseases virology, Virus Physiological Phenomena
Abstract

Viruses are genetically diverse, infect a wide range of tissues and host cells and follow unique processes for replicating themselves. All these processes were investigated and indexed in ViralZone knowledge base. To facilitate standardizing data, a simple ontology of viral life-cycle terms was developed to provide a common vocabulary for annotating data sets. New terminology was developed to address unique viral replication cycle processes, and existing terminology was modified and adapted. The virus life-cycle is classically described by schematic pictures. Using this ontology, it can be represented by a combination of successive terms: "entry", "latency", "transcription", "replication" and "exit". Each of these parts is broken down into discrete steps. For example Zika virus "entry" is broken down in successive steps: "Attachment", "Apoptotic mimicry", "Viral endocytosis/ macropinocytosis", "Fusion with host endosomal membrane", "Viral factory". To demonstrate the utility of a standard ontology for virus biology, this work was completed by annotating virus data in the ViralZone, UniProtKB and Gene Ontology databases.

Published
2017
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33. An integrated ontology resource to explore and study host-virus relationships.

Author

Masson P, Hulo C, de Castro E, Foulger R, Poux S, Bridge A, Lomax J, Bougueleret L, Xenarios I, and Le Mercier P

Subjects
Adaptive Immunity genetics, Animals, Databases, Nucleic Acid, Gene Expression Regulation immunology, Humans, Immunity, Innate, Interferons genetics, Virus Diseases genetics, Virus Diseases immunology, Virus Diseases virology, Gene Ontology, Host-Pathogen Interactions genetics
Abstract

Our growing knowledge of viruses reveals how these pathogens manage to evade innate host defenses. A global scheme emerges in which many viruses usurp key cellular defense mechanisms and often inhibit the same components of antiviral signaling. To accurately describe these processes, we have generated a comprehensive dictionary for eukaryotic host-virus interactions. This controlled vocabulary has been detailed in 57 ViralZone resource web pages which contain a global description of all molecular processes. In order to annotate viral gene products with this vocabulary, an ontology has been built in a hierarchy of UniProt Knowledgebase (UniProtKB) keyword terms and corresponding Gene Ontology (GO) terms have been developed in parallel. The results are 65 UniProtKB keywords related to 57 GO terms, which have been used in 14,390 manual annotations; 908,723 automatic annotations and propagated to an estimation of 922,941 GO annotations. ViralZone pages, UniProtKB keywords and GO terms provide complementary tools to users, and the three resources have been linked to each other through host-virus vocabulary.

Published
2014
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34. Nuclear phosphoinositides and their impact on nuclear functions.

Author

Shah ZH, Jones DR, Sommer L, Foulger R, Bultsma Y, D'Santos C, and Divecha N

Subjects
Animals, Cell Nucleus genetics, Humans, Cell Nucleus metabolism, Phosphatidylinositols metabolism, Signal Transduction
Abstract

Polyphosphoinositides (PPIn) are important lipid molecules whose levels are de-regulated in human diseases such as cancer, neurodegenerative disorders and metabolic syndromes. PPIn are synthesized and degraded by an array of kinases, phosphatases and lipases which are localized to various subcellular compartments and are subject to regulation in response to both extra- and intracellular cues. Changes in the activities of enzymes that metabolize PPIn lead to changes in the profiles of PPIn in various subcellular compartments. Understanding how subcellular PPIn are regulated and how they affect downstream signaling is critical to understanding their roles in human diseases. PPIn are present in the nucleus, and their levels are changed in response to various stimuli, suggesting that they may serve to regulate specific nuclear functions. However, the lack of nuclear downstream targets has hindered the definition of which pathways nuclear PPIn affect. Over recent years, targeted and global proteomic studies have identified a plethora of potential PPIn-interacting proteins involved in many aspects of transcription, chromatin remodelling and mRNA maturation, suggesting that PPIn signalling within the nucleus represents a largely unexplored novel layer of complexity in the regulation of nuclear functions., (© 2013 FEBS.)

Published
2013
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35. PtdIns5P is an oxidative stress-induced second messenger that regulates PKB activation.

Author

Jones DR, Foulger R, Keune WJ, Bultsma Y, and Divecha N

Subjects
3-Phosphoinositide-Dependent Protein Kinases, Cell Survival drug effects, Cells, Cultured, Enzyme Activation, Humans, Hydrogen Peroxide pharmacology, Oxidation-Reduction, Oxidative Stress drug effects, Phosphorylation, p38 Mitogen-Activated Protein Kinases metabolism, Oxidative Stress physiology, Phosphatidylinositol Phosphates metabolism, Protein Serine-Threonine Kinases metabolism, Second Messenger Systems physiology
Abstract

Oxidative stress initiates signaling pathways, which protect from stress-induced cellular damage, initiate apoptosis, or drive cells into senescence or into tumorigenesis. Oxidative stress regulates the activity of the cell survival factor PKB, through the regulation of PtdIns(3,4,5)P₃ synthesis. Whether oxidative stress regulates other phosphoinositides to control PKB activation is not clear. Here we show that PtdIns5P is a redox-regulated second messenger. In response to hydrogen peroxide (H₂O₂), we measured an increase in PtdIns5P in cells derived from human osteosarcoma, U2OS (5-fold); breast tumors, MDA-MB-468 (2-fold); and fibrosarcoma, HT1080 (3-fold); and in p53-null murine embryonic fibroblasts (8-fold). In U2OS cells, the increase in H₂O₂-dependent PtdIns5P did not require mTOR, PDK1, PKB, ERK, and p38 signaling or PIKfyve, a lipid kinase that increases PtdIns5P in response to osmotic and oncogenic signaling. A reduction in H₂O₂-induced PtdIns5P levels by the overexpression of PIP4K revealed its role in PKB activation. Suppression of H₂O₂-induced PtdIns5P generation reduced PKB activation and, surprisingly, reduced cell sensitivity to growth inhibition by H₂O₂. These data suggest that inhibition of PIP4K signaling might be useful as a novel strategy to increase the susceptibility of tumor cells to therapeutics that function through increased oxidative stress.

Published
2013
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36. The Gene Ontology (GO) database and informatics resource.

Author

Harris MA, Clark J, Ireland A, Lomax J, Ashburner M, Foulger R, Eilbeck K, Lewis S, Marshall B, Mungall C, Richter J, Rubin GM, Blake JA, Bult C, Dolan M, Drabkin H, Eppig JT, Hill DP, Ni L, Ringwald M, Balakrishnan R, Cherry JM, Christie KR, Costanzo MC, Dwight SS, Engel S, Fisk DG, Hirschman JE, Hong EL, Nash RS, Sethuraman A, Theesfeld CL, Botstein D, Dolinski K, Feierbach B, Berardini T, Mundodi S, Rhee SY, Apweiler R, Barrell D, Camon E, Dimmer E, Lee V, Chisholm R, Gaudet P, Kibbe W, Kishore R, Schwarz EM, Sternberg P, Gwinn M, Hannick L, Wortman J, Berriman M, Wood V, de la Cruz N, Tonellato P, Jaiswal P, Seigfried T, and White R

Subjects
Animals, Bibliographies as Topic, Electronic Mail, Genomics, Humans, Information Storage and Retrieval, Internet, Molecular Biology, Proteins classification, Proteins genetics, Software, Databases, Genetic, Genes, Terminology as Topic
Abstract

The Gene Ontology (GO) project (http://www. geneontology.org/) provides structured, controlled vocabularies and classifications that cover several domains of molecular and cellular biology and are freely available for community use in the annotation of genes, gene products and sequences. Many model organism databases and genome annotation groups use the GO and contribute their annotation sets to the GO resource. The GO database integrates the vocabularies and contributed annotations and provides full access to this information in several formats. Members of the GO Consortium continually work collectively, involving outside experts as needed, to expand and update the GO vocabularies. The GO Web resource also provides access to extensive documentation about the GO project and links to applications that use GO data for functional analyses.

Published
2004
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