Turning straw into gold : building robustness into gene signature inference

Reproducible and generalizable gene signatures are essential for clinical deployment, but are hard to come by. The primary issue is insufficient mitigation of confounders: ensuring that hypotheses are appropriate, test statistics and null distributions are appropriate, and so on. To further improve...

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Bibliographic Details
Main Authors: Goh, Wilson Wen Bin, Wong, Limsoon
Other Authors: School of Biological Sciences
Format: Journal Article
Language:English
Published: 2020
Subjects:
Online Access:https://hdl.handle.net/10356/137542
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author Goh, Wilson Wen Bin
Wong, Limsoon
author2 School of Biological Sciences
author_facet School of Biological Sciences
Goh, Wilson Wen Bin
Wong, Limsoon
author_sort Goh, Wilson Wen Bin
collection NTU
description Reproducible and generalizable gene signatures are essential for clinical deployment, but are hard to come by. The primary issue is insufficient mitigation of confounders: ensuring that hypotheses are appropriate, test statistics and null distributions are appropriate, and so on. To further improve robustness, additional good analytical practices (GAPs) are needed, namely: leveraging existing data and knowledge; careful and systematic evaluation of gene sets, even if they overlap with known sources of confounding; and rigorous testing of inferred signatures against as many published data sets as possible. Here, using a re-examination of a breast cancer data set and 48 published signatures, we illustrate the value of adopting these GAPs.
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spelling ntu-10356/1375422023-02-28T17:06:40Z Turning straw into gold : building robustness into gene signature inference Goh, Wilson Wen Bin Wong, Limsoon School of Biological Sciences Science::Biological sciences Good Analytical Practices Meta-analysis Reproducible and generalizable gene signatures are essential for clinical deployment, but are hard to come by. The primary issue is insufficient mitigation of confounders: ensuring that hypotheses are appropriate, test statistics and null distributions are appropriate, and so on. To further improve robustness, additional good analytical practices (GAPs) are needed, namely: leveraging existing data and knowledge; careful and systematic evaluation of gene sets, even if they overlap with known sources of confounding; and rigorous testing of inferred signatures against as many published data sets as possible. Here, using a re-examination of a breast cancer data set and 48 published signatures, we illustrate the value of adopting these GAPs. Accepted version 2020-04-01T04:39:33Z 2020-04-01T04:39:33Z 2018 Journal Article Goh, W. W. B., & Wong, L. (2019). Turning straw into gold : building robustness into gene signature inference. Drug Discovery Today, 24(1), 31-36. doi:10.1016/j.drudis.2018.08.002 1359-6446 https://hdl.handle.net/10356/137542 10.1016/j.drudis.2018.08.002 30081096 2-s2.0-85051501791 1 24 31 36 en Drug Discovery Today © 2018 Elsevier Ltd. All rights reserved. This paper was published in Drug Discovery Today and is made available with permission of Elsevier Ltd. application/pdf
spellingShingle Science::Biological sciences
Good Analytical Practices
Meta-analysis
Goh, Wilson Wen Bin
Wong, Limsoon
Turning straw into gold : building robustness into gene signature inference
title Turning straw into gold : building robustness into gene signature inference
title_full Turning straw into gold : building robustness into gene signature inference
title_fullStr Turning straw into gold : building robustness into gene signature inference
title_full_unstemmed Turning straw into gold : building robustness into gene signature inference
title_short Turning straw into gold : building robustness into gene signature inference
title_sort turning straw into gold building robustness into gene signature inference
topic Science::Biological sciences
Good Analytical Practices
Meta-analysis
url https://hdl.handle.net/10356/137542
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