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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Format: | Journal Article |
Language: | English |
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2020
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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. |
first_indexed | 2024-10-01T05:36:47Z |
format | Journal Article |
id | ntu-10356/137542 |
institution | Nanyang Technological University |
language | English |
last_indexed | 2024-10-01T05:36:47Z |
publishDate | 2020 |
record_format | dspace |
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 |
work_keys_str_mv | AT gohwilsonwenbin turningstrawintogoldbuildingrobustnessintogenesignatureinference AT wonglimsoon turningstrawintogoldbuildingrobustnessintogenesignatureinference |