Gene annotation bias impedes biomedical research

doi:10.1038/s41598-018-19333-x

. 2018 Jan 22;8(1):1362.

doi: 10.1038/s41598-018-19333-x.

Gene annotation bias impedes biomedical research

Winston A Haynes^{1

2

3}, Aurelie Tomczak^{1

2}, Purvesh Khatri^{4

5}

Affiliations

¹ Stanford Institute for Immunity, Transplantation, and Infection, Stanford University, Stanford, California, USA.
² Stanford Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, California, USA.
³ Biomedical Informatics Training Program, Stanford University, Stanford, California, USA.
⁴ Stanford Institute for Immunity, Transplantation, and Infection, Stanford University, Stanford, California, USA. pkhatri@stanford.edu.
⁵ Stanford Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, California, USA. pkhatri@stanford.edu.

PMID: 29358745
PMCID: PMC5778030
DOI: 10.1038/s41598-018-19333-x

Gene annotation bias impedes biomedical research

Winston A Haynes et al. Sci Rep. 2018.

. 2018 Jan 22;8(1):1362.

doi: 10.1038/s41598-018-19333-x.

Authors

Winston A Haynes^{1

2

3}, Aurelie Tomczak^{1

2}, Purvesh Khatri^{4

5}

Affiliations

¹ Stanford Institute for Immunity, Transplantation, and Infection, Stanford University, Stanford, California, USA.
² Stanford Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, California, USA.
³ Biomedical Informatics Training Program, Stanford University, Stanford, California, USA.
⁴ Stanford Institute for Immunity, Transplantation, and Infection, Stanford University, Stanford, California, USA. pkhatri@stanford.edu.
⁵ Stanford Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, California, USA. pkhatri@stanford.edu.

PMID: 29358745
PMCID: PMC5778030
DOI: 10.1038/s41598-018-19333-x

Abstract

We found tremendous inequality across gene and protein annotation resources. We observed that this bias leads biomedical researchers to focus on richly annotated genes instead of those with the strongest molecular data. We advocate that researchers reduce these biases by pursuing data-driven hypotheses.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

**Figure 1**
Inequality in gene annotations. (A) We measured the Gini coefficient across a variety of gene annotation resources. (B) We compared the growth in the Gini coefficient of the Gene Ontology to different models of increasing and decreasing inequality. See also Figure S1.

**Figure 2**
Published Disease-Gene Associations Not Reflected in Molecular Data. (A) The number of publications for every disease-gene pair was not significantly correlated with the gene expression multicohort analysis effect size FDR rank [Spearman’s correlation = −0.003, p = 0.836]. (B) The number of publications for every disease-gene pair correlated with the number of non-inferred from electronic annotation (non-IEA) Gene Ontology annotations [Spearman’s correlation = 0.110, p = 2.1e–16]. Orange points represent disease-gene associations published in our prior meta-analyses^,,. Purple points have at least 1000 publications. See also Figure S2.

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References

1. Khatri P, Sirota M, Butte AJ. Ten years of pathway analysis: current approaches and outstanding challenges. PLoS computational biology. 2012;8:e1002375. doi: 10.1371/journal.pcbi.1002375. - DOI - PMC - PubMed
1. Ashburner M, et al. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nature genetics. 2000;25:25–9. doi: 10.1038/75556. - DOI - PMC - PubMed
1. Croft D, et al. The Reactome pathway knowledgebase. Nucleic acids research. 2014;42:472–7. doi: 10.1093/nar/gkt1102. - DOI - PMC - PubMed
1. Davis AP, et al. The Comparative Toxicogenomics Database’s 10th year anniversary: update 2015. Nucleic acids research. 2015;43:914–20. doi: 10.1093/nar/gku935. - DOI - PMC - PubMed
1. Wishart DS, et al. DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucleic acids research. 2006;34:668–72. doi: 10.1093/nar/gkj067. - DOI - PMC - PubMed

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[1] Khatri P, Sirota M, Butte AJ. Ten years of pathway analysis: current approaches and outstanding challenges. PLoS computational biology. 2012;8:e1002375. doi: 10.1371/journal.pcbi.1002375. - DOI - PMC - PubMed

[2] Khatri P, Sirota M, Butte AJ. Ten years of pathway analysis: current approaches and outstanding challenges. PLoS computational biology. 2012;8:e1002375. doi: 10.1371/journal.pcbi.1002375. - DOI - PMC - PubMed

[3] Ashburner M, et al. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nature genetics. 2000;25:25–9. doi: 10.1038/75556. - DOI - PMC - PubMed

[4] Ashburner M, et al. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nature genetics. 2000;25:25–9. doi: 10.1038/75556. - DOI - PMC - PubMed

[5] Croft D, et al. The Reactome pathway knowledgebase. Nucleic acids research. 2014;42:472–7. doi: 10.1093/nar/gkt1102. - DOI - PMC - PubMed

[6] Croft D, et al. The Reactome pathway knowledgebase. Nucleic acids research. 2014;42:472–7. doi: 10.1093/nar/gkt1102. - DOI - PMC - PubMed

[7] Davis AP, et al. The Comparative Toxicogenomics Database’s 10th year anniversary: update 2015. Nucleic acids research. 2015;43:914–20. doi: 10.1093/nar/gku935. - DOI - PMC - PubMed

[8] Davis AP, et al. The Comparative Toxicogenomics Database’s 10th year anniversary: update 2015. Nucleic acids research. 2015;43:914–20. doi: 10.1093/nar/gku935. - DOI - PMC - PubMed

[9] Wishart DS, et al. DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucleic acids research. 2006;34:668–72. doi: 10.1093/nar/gkj067. - DOI - PMC - PubMed

[10] Wishart DS, et al. DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucleic acids research. 2006;34:668–72. doi: 10.1093/nar/gkj067. - DOI - PMC - PubMed

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Gene annotation bias impedes biomedical research

Affiliations

Gene annotation bias impedes biomedical research

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Affiliations

Abstract

Conflict of interest statement

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