Co-expression networks reveal the tissue-specific regulation of transcription and splicing

Abstract

Gene co-expression networks capture biologically important patterns in gene expression data, enabling functional analyses of genes, discovery of biomarkers, and interpretation of genetic variants. Most network analyses to date have been limited to assessing correlation between total gene expression levels in a single tissue or small sets of tissues. Here, we built networks that additionally capture the regulation of relative isoform abundance and splicing, along with tissue-specific connections unique to each of a diverse set of tissues. We used the Genotype-Tissue Expression (GTEx) project v6 RNA sequencing data across 50 tissues and 449 individuals. First, we developed a framework called Transcriptome-Wide Networks (TWNs) for combining total expression and relative isoform levels into a single sparse network, capturing the interplay between the regulation of splicing and transcription. We built TWNs for 16 tissues and found that hubs in these networks were strongly enriched for splicing and RNA binding genes, demonstrating their utility in unraveling regulation of splicing in the human transcriptome. Next, we used a Bayesian biclustering model that identifies network edges unique to a single tissue to reconstruct Tissue-Specific Networks (TSNs) for 26 distinct tissues and 10 groups of related tissues. Finally, we found genetic variants associated with pairs of adjacent nodes in our networks, supporting the estimated network structures and identifying 20 genetic variants with distant regulatory impact on transcription and splicing. Our networks provide an improved understanding of the complex relationships of the human transcriptome across tissues.

References 98

1. 1.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

2. 2.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

3. 3.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

4. 4.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

5. 5.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

6. 6.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

7. 7.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

8. 8.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

9. 9.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

10. 10.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

11. 11.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

12. 12.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

13. 13.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

14. 14.
    The Reactome pathway Knowledgebase · 2015

    No notice
15. 15.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

16. 16.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

17. 17.
    A Flexible and Accurate Genotype Imputation Method for the Next Generation of Genome-Wide Association Studies · 2009

    No notice
18. 18.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

19. 19.
    RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome · 2011

    No notice
20. 20.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

21. 21.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

22. 22.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

23. 23.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

24. 24.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

25. 25.
    Fast Computation and Applications of Genome Mappability · 2012

    No notice
26. 26.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

27. 27.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

28. 28.
    A Selected Core Microbiome Drives the Early Stages of Three Popular Italian Cheese Manufactures · 2014

    No notice
29. 29.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

30. 30.
    Transcriptome Sequencing Reveals Potential Mechanism of Cryptic 3’ Splice Site Selection in SF3B1-mutated Cancers · 2015

    No notice
31. 31.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

32. 32.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

33. 33.
    MTML-msBayes: Approximate Bayesian comparative phylogeographic inference from multiple taxa and multiple loci with rate heterogeneity · 2011

    No notice
34. 34.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

35. 35.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

36. 36.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

37. 37.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

38. 38.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

39. 39.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

40. 40.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

41. 41.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

42. 42.
    Understanding splicing regulation through RNA splicing maps · 2011

    No notice
43. 43.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

44. 44.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

45. 45.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

46. 46.
    Human Gene Coexpression Landscape: Confident Network Derived from Tissue Transcriptomic Profiles · 2008

    No notice
47. 47.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

48. 48.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

49. 49.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

50. 50.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

51. 51.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

52. 52.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

53. 53.
    Ten Years of Pathway Analysis: Current Approaches and Outstanding Challenges · 2012

    No notice
54. 54.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

55. 55.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

56. 56.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

57. 57.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

58. 58.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

59. 59.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

60. 60.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

61. 61.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

62. 62.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

63. 63.
    Ultrafast and memory-efficient alignment of short DNA sequences to the human genome · 2009

    No notice
64. 64.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

65. 65.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

66. 66.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

67. 67.
    Trimmomatic: a flexible trimmer for Illumina sequence data · 2014

    No notice
68. 68.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

69. 69.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

70. 70.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

71. 71.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

72. 72.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

73. 73.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

74. 74.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

75. 75.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

76. 76.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

77. 77.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

78. 78.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

79. 79.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

80. 80.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

81. 81.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

82. 82.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

83. 83.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

84. 84.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

85. 85.
    Alternative Splicing and Tumor Progression · 2008

    No notice
86. 86.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

87. 87.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

88. 88.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

89. 89.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

90. 90.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

91. 91.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

92. 92.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

93. 93.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

94. 94.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

95. 95.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

96. 96.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

97. 97.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

98. 98.
    Sharing and Specificity of Co-expression Networks across 35 Human Tissues · 2015

    No notice

Cited by papers we hold 5

• Evolution of a Landscape Phage Library in a Mouse Xenograft Model of Human Breast Cancer · 2019
  Not checked
• RNA-sequencing across three matched tissues reveals shared and tissue-specific gene expression and pathway signatures of COPD · 2019
  Not checked
• Network Medicine in the Age of Biomedical Big Data · 2019
  No notice
• When pitch adds to volume: coregulation of transcript diversity predicts gene function · 2018
  Not checked
• Genetic effects on gene expression across human tissues · 2017
  Corrected

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.