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J Biol Rhythms. 2017 Oct;32(5):380-393. doi: 10.1177/0748730417728663. Epub 2017 Nov 3.

Guidelines for Genome-Scale Analysis of Biological Rhythms.

Author information

1
1 Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
2
2 Department of Biology and Howard Hughes Medical Institute, Brandeis University, Waltham, Massachusetts, USA.
3
3 Department of Neurobiology, Northwestern University, Evanston, Illinois, USA.
4
4 Division of Sleep Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, USA.
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5 Center for Integrative Genomics, Génopode, University of Lausanne, Lausanne, Switzerland.
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6 Vital-IT, Swiss Institute of Bioinformatics, Lausanne, Switzerland.
7
7 Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
8
8 Institute for Genomics and Bioinformatics, University of California, Irvine, USA.
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9 Department of Biology, University of Central Florida, Orlando, USA.
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10 Department of Biology, Texas A&M University, College Station, USA.
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11 Department of Biology, New York University, New York, USA.
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12 Institute of Pharmacology and Toxicology, University of Zürich, Switzerland.
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13 Laboratorio de Genética del Comportamiento, Fundación Instituto Leloir, IIBBA-CONICET, Buenos Aires, Argentina.
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14 Department of Biochemistry and Molecular Biology, University of Texas Health Science Center, Houston, USA.
15
15 Department of Entomology and Nematology, University of California, Davis, USA.
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16 Computational Systems Biochemistry, Max-Planck Institute of Biochemistry, Martinsried, Germany.
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17 Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.
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18 Department of Pharmacology and Toxicology, Morehouse School of Medicine, Atlanta, Georgia, USA.
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19 Surrey Sleep Research Centre, University of Surrey, Guildford, UK.
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20 The University of Kansas Medical Center, University of Kansas, Kansas City, USA.
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21 John A. Paulson School of Engineering and Applied Sciences, Harvard University, Boston, Massachusetts, USA.
22
22 Department of Biological Sciences and Eck Institute for Global Health, University of Notre Dame, Notre Dame, Indiana, USA.
23
23 Institute of Molecular Medicine, McGovern Medical School, UT Health Houston, Houston, Texas, USA.
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24 Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, USA.
25
25 Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, USA.
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26 Department of Mathematics, University of Michigan, Ann Arbor, USA.
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27 Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
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28 Kavli Institute for Fundamental Neuroscience, Weill Institute of Neuroscience, Department of Neurology, University of California, San Francisco, USA.
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29 Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, Lausanne, Switzerland.
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30 Department of Endocrinology & Metabolism, Academic Medical Center, Amsterdam, the Netherlands.
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31 Center for Circadian Biology and Division of Biological Sciences, University of California, San Diego, La Jolla, USA.
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32 Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, USA.
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33 Department of Mathematics, Duke University, Durham, North Carolina, USA.
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34 Department of Plant Biology, University of California, Davis, USA.
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35 Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
36
36 Institute for Theoretical Biology, Charité-Universitätsmedizin Berlin, Germany.
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37 Department of Biology, Washington University in St. Louis, Missouri, USA.
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38 Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
39
39 Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, New York, USA.
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40 Department of Biology, University of Washington, Seattle, USA.
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41 Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, USA.
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42 Department of Cell and Molecular Biology, The Scripps Research Institute, University of California, San Diego, La Jolla, USA.
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43 Department of Physiology and Systems Bioscience, Kyoto Prefectural University of Medicine, Japan.
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44 Division of Sensory Biophysics, The Ohio State University, Columbus, USA.
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45 Laboratory of Chronobiology, Charité Universitätsmedizin Berlin, Germany.
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46 Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA.
47
47 Department of Mathematics and Statistics, Amherst College, Amherst, Massachusetts, USA.
48
48 Department of Biology, University of Missouri-St. Louis, USA.
49
49 Department of Cell Biology, College of Life Sciences at Wuhan University, China.
50
50 Department of Biological Sciences, University of Memphis, Tennessee, USA.
51
51 Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.
52
52 Centre for Cardiovascular Investigations, Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, Canada.
53
53 Institute of Medical Psychology, Faculty of Medicine, LMU Munich, Germany.
54
54 SynthSys and School of Biological Sciences, University of Edinburgh, UK.
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55 Donald Danforth Plant Science Center, St. Louis, Missouri, USA.
56
56 The Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Switzerland.
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57 Department of Genetics and Evolution, University of Geneva, Switzerland.
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58 Department of Cellular and Molecular Physiology, Department of Genetics, Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, Connecticut, USA.
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59 Department of Genetics, University of Seville, Spain.
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60 Department of Neurology, University of California, San Francisco, USA.
61
61 Warwick Systems Biology and Mathematics Institute, University of Warwick, Conventry, UK.
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62 The Francis Crick Institute, London, UK, and UCL Institute of Neurology, Queen Square, London, UK.
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63 Centre for Immunity, Infection and Evolution, University of Edinburgh, UK.
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64 Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, USA.
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65 Department of Biological Chemistry, Center for Epigenetics and Metabolism, University of California, Irvine, USA.
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66 Howard Hughes Medical Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, USA.
67
67 Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, USA.
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68 Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.
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69 Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Canada.
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70 Howard Hughes Medical Institute, Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, USA.
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71 Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Laboratory for Synthetic Biology, RIKEN Quantitative Biology Center, Osaka, Japan.
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72 Center for Circadian Clocks, Soochow University, Suzhou, Jiangsu, China.
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73 Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA.
74
74 Institute of Genetics and Biometry, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany.
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75 Biological Sciences and Institute for Life Sciences, University of Southampton, UK.
76
76 Cam-Su GRC, Soochow University, Suzhou, China.
77
77 Laboratory of Genetics, Rockefeller University, New York, New York, USA.
78
78 National Institute of Biological Sciences, Beijing, China.

Abstract

Genome biology approaches have made enormous contributions to our understanding of biological rhythms, particularly in identifying outputs of the clock, including RNAs, proteins, and metabolites, whose abundance oscillates throughout the day. These methods hold significant promise for future discovery, particularly when combined with computational modeling. However, genome-scale experiments are costly and laborious, yielding "big data" that are conceptually and statistically difficult to analyze. There is no obvious consensus regarding design or analysis. Here we discuss the relevant technical considerations to generate reproducible, statistically sound, and broadly useful genome-scale data. Rather than suggest a set of rigid rules, we aim to codify principles by which investigators, reviewers, and readers of the primary literature can evaluate the suitability of different experimental designs for measuring different aspects of biological rhythms. We introduce CircaInSilico, a web-based application for generating synthetic genome biology data to benchmark statistical methods for studying biological rhythms. Finally, we discuss several unmet analytical needs, including applications to clinical medicine, and suggest productive avenues to address them.

KEYWORDS:

ChIP-seq; RNA-seq; biostatistics; circadian rhythms; computational biology; diurnal rhythms; functional genomics; guidelines; metabolomics; proteomics; systems biology

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