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  1. Article ; Online: Lifespan-extending interventions induce consistent patterns of fatty acid oxidation in mouse livers

    Kengo Watanabe / Tomasz Wilmanski / Priyanka Baloni / Max Robinson / Gonzalo G. Garcia / Michael R. Hoopmann / Mukul K. Midha / David H. Baxter / Michal Maes / Seamus R. Morrone / Kelly M. Crebs / Charu Kapil / Ulrike Kusebauch / Jack Wiedrick / Jodi Lapidus / Lance Pflieger / Christopher Lausted / Jared C. Roach / Gwênlyn Glusman /
    Steven R. Cummings / Nicholas J. Schork / Nathan D. Price / Leroy Hood / Richard A. Miller / Robert L. Moritz / Noa Rappaport

    Communications Biology, Vol 6, Iss 1, Pp 1-

    2023  Volume 15

    Abstract: Abstract Aging manifests as progressive deteriorations in homeostasis, requiring systems-level perspectives to investigate the gradual molecular dysregulation of underlying biological processes. Here, we report systemic changes in the molecular ... ...

    Abstract Abstract Aging manifests as progressive deteriorations in homeostasis, requiring systems-level perspectives to investigate the gradual molecular dysregulation of underlying biological processes. Here, we report systemic changes in the molecular regulation of biological processes under multiple lifespan-extending interventions. Differential Rank Conservation (DIRAC) analyses of mouse liver proteomics and transcriptomics data show that mechanistically distinct lifespan-extending interventions (acarbose, 17α-estradiol, rapamycin, and calorie restriction) generally tighten the regulation of biological modules. These tightening patterns are similar across the interventions, particularly in processes such as fatty acid oxidation, immune response, and stress response. Differences in DIRAC patterns between proteins and transcripts highlight specific modules which may be tightened via augmented cap-independent translation. Moreover, the systemic shifts in fatty acid metabolism are supported through integrated analysis of liver transcriptomics data with a mouse genome-scale metabolic model. Our findings highlight the power of systems-level approaches for identifying and characterizing the biological processes involved in aging and longevity.
    Keywords Biology (General) ; QH301-705.5
    Subject code 612
    Language English
    Publishing date 2023-07-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Author Correction

    Kengo Watanabe / Tomasz Wilmanski / Priyanka Baloni / Max Robinson / Gonzalo G. Garcia / Michael R. Hoopmann / Mukul K. Midha / David H. Baxter / Michal Maes / Seamus R. Morrone / Kelly M. Crebs / Charu Kapil / Ulrike Kusebauch / Jack Wiedrick / Jodi Lapidus / Lance Pflieger / Christopher Lausted / Jared C. Roach / Gwênlyn Glusman /
    Steven R. Cummings / Nicholas J. Schork / Nathan D. Price / Leroy Hood / Richard A. Miller / Robert L. Moritz / Noa Rappaport

    Communications Biology, Vol 6, Iss 1, Pp 1-

    Lifespan-extending interventions induce consistent patterns of fatty acid oxidation in mouse livers

    2023  Volume 1

    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2023-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Accurate and robust prediction of genetic relationship from whole-genome sequences.

    Hong Li / Gustavo Glusman / Chad Huff / Juan Caballero / Jared C Roach

    PLoS ONE, Vol 9, Iss 2, p e

    2014  Volume 85437

    Abstract: Computing the genetic relationship between two humans is important to studies in genetics, genomics, genealogy, and forensics. Relationship algorithms may be sensitive to noise, such as that arising from sequencing errors or imperfect reference genomes. ... ...

    Abstract Computing the genetic relationship between two humans is important to studies in genetics, genomics, genealogy, and forensics. Relationship algorithms may be sensitive to noise, such as that arising from sequencing errors or imperfect reference genomes. We developed an algorithm for estimation of genetic relationship by averaged blocks (GRAB) that is designed for whole-genome sequencing (WGS) data. GRAB segments the genome into blocks, calculates the fraction of blocks sharing identity, and then uses a classification tree to infer 1st- to 5th- degree relationships and unrelated individuals. We evaluated GRAB on simulated and real sequenced families, and compared it with other software. GRAB achieves similar performance, and does not require knowledge of population background or phasing. GRAB can be used in workflows for identifying unreported relationships, validating reported relationships in family-based studies, and detection of sample-tracking errors or duplicate inclusion. The software is available at familygenomics.systemsbiology.net/grab.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Author Correction

    Liping Hou / Rachel L. Kember / Jared C. Roach / Jeffrey R. O’Connell / David W. Craig / Maja Bucan / William K. Scott / Margaret Pericak-Vance / Jonathan L. Haines / Michael H. Crawford / Alan R. Shuldiner / Francis J. McMahon

    Scientific Reports, Vol 8, Iss 1, Pp 1-

    A population-specific reference panel empowers genetic studies of Anabaptist populations

    2018  Volume 1

    Abstract: A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper. ...

    Abstract A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2018-04-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: A population-specific reference panel empowers genetic studies of Anabaptist populations

    Liping Hou / Rachel L. Kember / Jared C. Roach / Jeffrey R. O’Connell / David W. Craig / Maja Bucan / William K. Scott / Margaret Pericak-Vance / Jonathan L. Haines / Michael H. Crawford / Alan R. Shuldiner / Francis J. McMahon

    Scientific Reports, Vol 7, Iss 1, Pp 1-

    2017  Volume 9

    Abstract: Abstract Genotype imputation is a powerful strategy for achieving the large sample sizes required for identification of variants underlying complex phenotypes, but imputation of rare variants remains problematic. Genetically isolated populations offer ... ...

    Abstract Abstract Genotype imputation is a powerful strategy for achieving the large sample sizes required for identification of variants underlying complex phenotypes, but imputation of rare variants remains problematic. Genetically isolated populations offer one solution, however population-specific reference panels are needed to assure optimal imputation accuracy and allele frequency estimation. Here we report the Anabaptist Genome Reference Panel (AGRP), the first whole-genome catalogue of variants and phased haplotypes in people of Amish and Mennonite ancestry. Based on high-depth whole-genome sequence (WGS) from 265 individuals, the AGRP contains >12 M high-confidence single nucleotide variants and short indels, of which ~12.5% are novel. These Anabaptist-specific variants were more deleterious than variants with comparable frequencies observed in the 1000 Genomes panel. About 43,000 variants showed enriched allele frequencies in AGRP, consistent with drift. When combined with the 1000 Genomes Project reference panel, the AGRP substantially improved imputation, especially for rarer variants. The AGRP is freely available to researchers through an imputation server.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2017-07-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Whole-genome sequencing of the world's oldest people.

    Hinco J Gierman / Kristen Fortney / Jared C Roach / Natalie S Coles / Hong Li / Gustavo Glusman / Glenn J Markov / Justin D Smith / Leroy Hood / L Stephen Coles / Stuart K Kim

    PLoS ONE, Vol 9, Iss 11, p e

    2014  Volume 112430

    Abstract: Supercentenarians (110 years or older) are the world's oldest people. Seventy four are alive worldwide, with twenty two in the United States. We performed whole-genome sequencing on 17 supercentenarians to explore the genetic basis underlying extreme ... ...

    Abstract Supercentenarians (110 years or older) are the world's oldest people. Seventy four are alive worldwide, with twenty two in the United States. We performed whole-genome sequencing on 17 supercentenarians to explore the genetic basis underlying extreme human longevity. We found no significant evidence of enrichment for a single rare protein-altering variant or for a gene harboring different rare protein altering variants in supercentenarian compared to control genomes. We followed up on the gene most enriched for rare protein-altering variants in our cohort of supercentenarians, TSHZ3, by sequencing it in a second cohort of 99 long-lived individuals but did not find a significant enrichment. The genome of one supercentenarian had a pathogenic mutation in DSC2, known to predispose to arrhythmogenic right ventricular cardiomyopathy, which is recommended to be reported to this individual as an incidental finding according to a recent position statement by the American College of Medical Genetics and Genomics. Even with this pathogenic mutation, the proband lived to over 110 years. The entire list of rare protein-altering variants and DNA sequence of all 17 supercentenarian genomes is available as a resource to assist the discovery of the genetic basis of extreme longevity in future studies.
    Keywords Medicine ; R ; Science ; Q
    Subject code 572
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article: TFCat: the curated catalog of mouse and human transcription factors

    Fulton, Debra L / Gwenael Badis / Jared C Roach / Rob Sladek / Saravanan Sundararajan / Timothy R Hughes / Wyeth W Wasserman

    Genome biology. 2009 Mar., v. 10, no. 3

    2009  

    Abstract: Unravelling regulatory programs governed by transcription factors (TFs) is fundamental to understanding biological systems. TFCat is a catalog of mouse and human TFs based on a reliable core collection of annotations obtained by expert review of the ... ...

    Abstract Unravelling regulatory programs governed by transcription factors (TFs) is fundamental to understanding biological systems. TFCat is a catalog of mouse and human TFs based on a reliable core collection of annotations obtained by expert review of the scientific literature. The collection, including proven and homology-based candidate TFs, is annotated within a function-based taxonomy and DNA-binding proteins are organized within a classification system. All data and user-feedback mechanisms are available at the TFCat portal http://www.tfcat.ca .
    Keywords DNA-binding proteins ; humans ; mice ; taxonomy ; transcription factors
    Language English
    Dates of publication 2009-03
    Size p. 2179.
    Publishing place Springer-Verlag
    Document type Article
    ZDB-ID 2040529-7
    ISSN 1474-760X ; 1465-6914 ; 1465-6906
    ISSN (online) 1474-760X ; 1465-6914
    ISSN 1465-6906
    DOI 10.1186/gb-2009-10-3-r29
    Database NAL-Catalogue (AGRICOLA)

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  8. Article ; Online: A third approach to gene prediction suggests thousands of additional human transcribed regions.

    Gustavo Glusman / Shizhen Qin / M Raafat El-Gewely / Andrew F Siegel / Jared C Roach / Leroy Hood / Arian F A Smit

    PLoS Computational Biology, Vol 2, Iss 3, p e

    2006  Volume 18

    Abstract: The identification and characterization of the complete ensemble of genes is a main goal of deciphering the digital information stored in the human genome. Many algorithms for computational gene prediction have been described, ultimately derived from two ...

    Abstract The identification and characterization of the complete ensemble of genes is a main goal of deciphering the digital information stored in the human genome. Many algorithms for computational gene prediction have been described, ultimately derived from two basic concepts: (1) modeling gene structure and (2) recognizing sequence similarity. Successful hybrid methods combining these two concepts have also been developed. We present a third orthogonal approach to gene prediction, based on detecting the genomic signatures of transcription, accumulated over evolutionary time. We discuss four algorithms based on this third concept: Greens and CHOWDER, which quantify mutational strand biases caused by transcription-coupled DNA repair, and ROAST and PASTA, which are based on strand-specific selection against polyadenylation signals. We combined these algorithms into an integrated method called FEAST, which we used to predict the location and orientation of thousands of putative transcription units not overlapping known genes. Many of the newly predicted transcriptional units do not appear to code for proteins. The new algorithms are particularly apt at detecting genes with long introns and lacking sequence conservation. They therefore complement existing gene prediction methods and will help identify functional transcripts within many apparent "genomic deserts."
    Keywords Biology (General) ; QH301-705.5
    Subject code 004
    Language English
    Publishing date 2006-03-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: High functional diversity in Mycobacterium tuberculosis driven by genetic drift and human demography.

    Ruth Hershberg / Mikhail Lipatov / Peter M Small / Hadar Sheffer / Stefan Niemann / Susanne Homolka / Jared C Roach / Kristin Kremer / Dmitri A Petrov / Marcus W Feldman / Sebastien Gagneux

    PLoS Biology, Vol 6, Iss 12, p e

    2008  Volume 311

    Abstract: Mycobacterium tuberculosis infects one third of the human world population and kills someone every 15 seconds. For more than a century, scientists and clinicians have been distinguishing between the human- and animal-adapted members of the M. ... ...

    Abstract Mycobacterium tuberculosis infects one third of the human world population and kills someone every 15 seconds. For more than a century, scientists and clinicians have been distinguishing between the human- and animal-adapted members of the M. tuberculosis complex (MTBC). However, all human-adapted strains of MTBC have traditionally been considered to be essentially identical. We surveyed sequence diversity within a global collection of strains belonging to MTBC using seven megabase pairs of DNA sequence data. We show that the members of MTBC affecting humans are more genetically diverse than generally assumed, and that this diversity can be linked to human demographic and migratory events. We further demonstrate that these organisms are under extremely reduced purifying selection and that, as a result of increased genetic drift, much of this genetic diversity is likely to have functional consequences. Our findings suggest that the current increases in human population, urbanization, and global travel, combined with the population genetic characteristics of M. tuberculosis described here, could contribute to the emergence and spread of drug-resistant tuberculosis.
    Keywords Biology (General) ; QH301-705.5
    Subject code 006
    Language English
    Publishing date 2008-12-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Alternating Hemiplegia of Childhood

    Louis Viollet / Gustavo Glusman / Kelley J Murphy / Tara M Newcomb / Sandra P Reyna / Matthew Sweney / Benjamin Nelson / Frederick Andermann / Eva Andermann / Gyula Acsadi / Richard L Barbano / Candida Brown / Mary E Brunkow / Harry T Chugani / Sarah R Cheyette / Abigail Collins / Suzanne D DeBrosse / David Galas / Jennifer Friedman /
    Lee Hood / Chad Huff / Lynn B Jorde / Mary D King / Bernie LaSalle / Richard J Leventer / Aga J Lewelt / Mylynda B Massart / Mario R Mérida / Louis J Ptáček / Jared C Roach / Robert S Rust / Francis Renault / Terry D Sanger / Marcio A Sotero de Menezes / Rachel Tennyson / Peter Uldall / Yue Zhang / Mary Zupanc / Winnie Xin / Kenneth Silver / Kathryn J Swoboda

    PLoS ONE, Vol 10, Iss 5, p e

    Retrospective Genetic Study and Genotype-Phenotype Correlations in 187 Subjects from the US AHCF Registry.

    2015  Volume 0127045

    Abstract: Mutations in ATP1A3 cause Alternating Hemiplegia of Childhood (AHC) by disrupting function of the neuronal Na+/K+ ATPase. Published studies to date indicate 2 recurrent mutations, D801N and E815K, and a more severe phenotype in the E815K cohort. We ... ...

    Abstract Mutations in ATP1A3 cause Alternating Hemiplegia of Childhood (AHC) by disrupting function of the neuronal Na+/K+ ATPase. Published studies to date indicate 2 recurrent mutations, D801N and E815K, and a more severe phenotype in the E815K cohort. We performed mutation analysis and retrospective genotype-phenotype correlations in all eligible patients with AHC enrolled in the US AHC Foundation registry from 1997-2012. Clinical data were abstracted from standardized caregivers' questionnaires and medical records and confirmed by expert clinicians. We identified ATP1A3 mutations by Sanger and whole genome sequencing, and compared phenotypes within and between 4 groups of subjects, those with D801N, E815K, other ATP1A3 or no ATP1A3 mutations. We identified heterozygous ATP1A3 mutations in 154 of 187 (82%) AHC patients. Of 34 unique mutations, 31 (91%) are missense, and 16 (47%) had not been previously reported. Concordant with prior studies, more than 2/3 of all mutations are clusteredin exons 17 and 18. Of 143 simplex occurrences, 58 had D801N (40%), 38 had E815K(26%) and 11 had G947R (8%) mutations [corrected].Patients with an E815K mutation demonstrate an earlier age of onset, more severe motor impairment and a higher prevalence of status epilepticus. This study further expands the number and spectrum of ATP1A3 mutations associated with AHC and confirms a more deleterious effect of the E815K mutation on selected neurologic outcomes. However, the complexity of the disorder and the extensive phenotypic variability among subgroups merits caution and emphasizes the need for further studies.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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