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Somatic sequencing is among the primary applications of NGS, where acquired (non-inherited) variants are based on comparing diseased and healthy tissues from the same individual. Somatic mutations in genetic diseases such as cancer are tightly associated with genomic instability. Genomic instability increases heterogenity, complicating sequencing efforts further, a task already challenged by the presence of short reads and repetitions in human DNA. This leads to low concordance among studies and limits reproducibility. This limitation is a significant problem since identified mutations in somatic sequencing are major biomarkers for diagnosis and the primary input of targeted therapies. Benchmarking studies were conducted to assess the error rates and increase reproducibility. Unfortunately, the number of somatic benchmarking sets is very limited due to difficulties in validating true somatic variants. Moreover, most NGS benchmarking studies are based on relatively simpler germline (inherited) sequencing. Recently, a comprehensive somatic sequencing benchmarking set was published by Sequencing Quality Control Phase 2 (SEQC2). We chose this dataset for our experiments because it is a well-validated, cancer-focused dataset that includes many tumor\/normal biological replicates. Our study has two primary goals. First goal is to determine how replicate-based consensus approaches can improve the accuracy of somatic variant detection systems. Second goal is to develop highly predictive machine learning (ML) models by employing replicate-based consensus variants as labels during the training phase.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Ensemble approaches that combine alternative algorithms are relatively common; here, as an alternative, we study the performance enhancement potential of biological replicates. We first developed replicate-based consensus approaches that utilize the biological replicates available in this study to improve variant calling performance. Subsequently, we trained ML models using these biological replicates and achieved performance comparable to optimal ML models, those trained using high-confidence variants identified in advance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our replicate-based consensus approach can be used to improve variant calling performance and develop efficient ML models. Given the relative ease of obtaining biological replicates, this strategy allows for the development of efficient ML models tailored to specific datasets or scenarios.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12859-024-05742-5","type":"journal-article","created":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T04:24:27Z","timestamp":1711081467000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Improving somatic exome sequencing performance by biological replicates"],"prefix":"10.1186","volume":"25","author":[{"given":"Yunus Emre","family":"Cebeci","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rumeysa Aslihan","family":"Erturk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehmet Arif","family":"Ergun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehmet","family":"Baysan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,3,22]]},"reference":[{"issue":"7676","key":"5742_CR1","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1038\/nature24286","volume":"550","author":"J Shendure","year":"2017","unstructured":"Shendure J, et al. 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