Batch effects in population genomic studies with low‐coverage whole genome sequencing data: Causes, detection and mitigation
Abstract Over the past few decades, there has been an explosion in the amount of publicly available sequencing data. This opens new opportunities for combining data sets to achieve unprecedented sample sizes, spatial coverage or temporal replication in population genomic studies. However, a common c...
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crwiley:10.1111/1755-0998.13559 2024-06-02T08:03:13+00:00 Batch effects in population genomic studies with low‐coverage whole genome sequencing data: Causes, detection and mitigation Lou, Runyang Nicolas Therkildsen, Nina Overgaard National Science Foundation 2021 http://dx.doi.org/10.1111/1755-0998.13559 https://onlinelibrary.wiley.com/doi/pdf/10.1111/1755-0998.13559 https://onlinelibrary.wiley.com/doi/full-xml/10.1111/1755-0998.13559 https://onlinelibrary.wiley.com/doi/am-pdf/10.1111/1755-0998.13559 en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#am http://onlinelibrary.wiley.com/termsAndConditions#vor Molecular Ecology Resources volume 22, issue 5, page 1678-1692 ISSN 1755-098X 1755-0998 journal-article 2021 crwiley https://doi.org/10.1111/1755-0998.13559 2024-05-03T11:03:54Z Abstract Over the past few decades, there has been an explosion in the amount of publicly available sequencing data. This opens new opportunities for combining data sets to achieve unprecedented sample sizes, spatial coverage or temporal replication in population genomic studies. However, a common concern is that nonbiological differences between data sets may generate patterns of variation in the data that can confound real biological patterns, a problem known as batch effects. In this paper, we compare two batches of low‐coverage whole genome sequencing (lcWGS) data generated from the same populations of Atlantic cod ( Gadus morhua ). First, we show that with a “batch‐effect‐naive” bioinformatic pipeline, batch effects systematically biased our genetic diversity estimates, population structure inference and selection scans. We then demonstrate that these batch effects resulted from multiple technical differences between our data sets, including the sequencing chemistry (four‐channel vs. two‐channel), sequencing run, read type (single‐end vs. paired‐end), read length (125 vs. 150 bp), DNA degradation level (degraded vs. well preserved) and sequencing depth (0.8× vs. 0.3× on average). Lastly, we illustrate that a set of simple bioinformatic strategies (such as different read trimming and single nucleotide polymorphism filtering) can be used to detect batch effects in our data and substantially mitigate their impact. We conclude that combining data sets remains a powerful approach as long as batch effects are explicitly accounted for. We focus on lcWGS data in this paper, which may be particularly vulnerable to certain causes of batch effects, but many of our conclusions also apply to other sequencing strategies. Article in Journal/Newspaper atlantic cod Gadus morhua Wiley Online Library Molecular Ecology Resources 22 5 1678 1692 |
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English |
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Abstract Over the past few decades, there has been an explosion in the amount of publicly available sequencing data. This opens new opportunities for combining data sets to achieve unprecedented sample sizes, spatial coverage or temporal replication in population genomic studies. However, a common concern is that nonbiological differences between data sets may generate patterns of variation in the data that can confound real biological patterns, a problem known as batch effects. In this paper, we compare two batches of low‐coverage whole genome sequencing (lcWGS) data generated from the same populations of Atlantic cod ( Gadus morhua ). First, we show that with a “batch‐effect‐naive” bioinformatic pipeline, batch effects systematically biased our genetic diversity estimates, population structure inference and selection scans. We then demonstrate that these batch effects resulted from multiple technical differences between our data sets, including the sequencing chemistry (four‐channel vs. two‐channel), sequencing run, read type (single‐end vs. paired‐end), read length (125 vs. 150 bp), DNA degradation level (degraded vs. well preserved) and sequencing depth (0.8× vs. 0.3× on average). Lastly, we illustrate that a set of simple bioinformatic strategies (such as different read trimming and single nucleotide polymorphism filtering) can be used to detect batch effects in our data and substantially mitigate their impact. We conclude that combining data sets remains a powerful approach as long as batch effects are explicitly accounted for. We focus on lcWGS data in this paper, which may be particularly vulnerable to certain causes of batch effects, but many of our conclusions also apply to other sequencing strategies. |
author2 |
National Science Foundation |
format |
Article in Journal/Newspaper |
author |
Lou, Runyang Nicolas Therkildsen, Nina Overgaard |
spellingShingle |
Lou, Runyang Nicolas Therkildsen, Nina Overgaard Batch effects in population genomic studies with low‐coverage whole genome sequencing data: Causes, detection and mitigation |
author_facet |
Lou, Runyang Nicolas Therkildsen, Nina Overgaard |
author_sort |
Lou, Runyang Nicolas |
title |
Batch effects in population genomic studies with low‐coverage whole genome sequencing data: Causes, detection and mitigation |
title_short |
Batch effects in population genomic studies with low‐coverage whole genome sequencing data: Causes, detection and mitigation |
title_full |
Batch effects in population genomic studies with low‐coverage whole genome sequencing data: Causes, detection and mitigation |
title_fullStr |
Batch effects in population genomic studies with low‐coverage whole genome sequencing data: Causes, detection and mitigation |
title_full_unstemmed |
Batch effects in population genomic studies with low‐coverage whole genome sequencing data: Causes, detection and mitigation |
title_sort |
batch effects in population genomic studies with low‐coverage whole genome sequencing data: causes, detection and mitigation |
publisher |
Wiley |
publishDate |
2021 |
url |
http://dx.doi.org/10.1111/1755-0998.13559 https://onlinelibrary.wiley.com/doi/pdf/10.1111/1755-0998.13559 https://onlinelibrary.wiley.com/doi/full-xml/10.1111/1755-0998.13559 https://onlinelibrary.wiley.com/doi/am-pdf/10.1111/1755-0998.13559 |
genre |
atlantic cod Gadus morhua |
genre_facet |
atlantic cod Gadus morhua |
op_source |
Molecular Ecology Resources volume 22, issue 5, page 1678-1692 ISSN 1755-098X 1755-0998 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#am http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1111/1755-0998.13559 |
container_title |
Molecular Ecology Resources |
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22 |
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5 |
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1678 |
op_container_end_page |
1692 |
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1800747690492952576 |