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Method: A Bayesian framework to study tumor subclone–specific expression by combining bulk DNA and single-cell RNA sequencing data
- Yi Qiao,
- Xiaomeng Huang,
- Philip J. Moos,
- Jonathan M. Ahmann,
- Anthony D. Pomicter,
- Michael W. Deininger,
- John C. Byrd,
- Jennifer A. Woyach,
- Deborah M. Stephens,
- and Gabor T. Marth
Genome Res. January 2024 34: 94-105; Published in Advance January 9, 2024, doi:10.1101/gr.278234.123
...and its evolution over time and space within a patient, using somatic tumor mutation allele frequencies measured in bulk DNA sequencing data. Whereas the tumor mutations gleaned from bulk DNA sequencing can be used to define the genetic subclones and map out their evolutionary trajectory, functional (e...
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Method: Genome-wide maps of CPD deamination in yeast reveal the impact of DNA sequence context and nucleosome architecture on cytosine deamination rates
- Marian F. Laughery,
- Bastian Stark,
- Benjamin Morledge-Hampton,
- Steven A. Roberts,
- and John J. Wyrick
Genome Res. January 2026 36: 183-196; Published in Advance December 9, 2025, doi:10.1101/gr.280384.124
...and Wyrick 2024). To account for this potential confounding factor, we used a published CPD-seq data set derived from melanoma cells that had been irradiated with UVB light (Lindberg et al. 2019), and compared the frequency of CPDs in this data set to the frequency of somatic mutations across different...
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Research: Cellular age explains variation in age-related cell-to-cell transcriptome variability
- Ming Yang,
- Benjamin R. Harrison,
- and Daniel E.L. Promislow
Genome Res. November 2023 33: 1906-1916; Published in Advance November 16, 2023, doi:10.1101/gr.278144.123
...further show that long-lived cells are characterized by relatively high expression of genes associated with proteostasis and that the transcriptome of long-lived cells shows greater evolutionary constraint than short-lived cells. In contrast, in short-lived cell types, the transcriptome is enriched...
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Research: Whole genome sequencing of matched primary and metastatic acral melanomas
- Samra Turajlic,
- Simon J. Furney,
- Maryou B. Lambros,
- Costas Mitsopoulos,
- Iwanka Kozarewa,
- Felipe C. Geyer,
- Alan MacKay,
- Jarle Hakas,
- Marketa Zvelebil,
- Christopher J. Lord,
- Alan Ashworth,
- Meirion Thomas,
- Gordon Stamp,
- James Larkin,
- Jorge S. Reis-Filho,
- and Richard Marais
Genome Res. February 2012 22: 196-207; Published in Advance December 19, 2011, doi:10.1101/gr.125591.111
...variants byNGS butwere present in the germline by Sanger sequencing were classified as germline SNVs. We identified a total of 40 somatic nonsynonymous SNVs in the primary tumor and 41 somatic nonsynonymous SNVs and one splice site variant in the metastasis. The range of mutant allele frequencies was 21...
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Research: APOBEC3A drives deaminase mutagenesis in human gastric epithelium
- Yohan An,
- Ji-Hyun Lee,
- Joonoh Lim,
- Jeonghwan Youk,
- Seongyeol Park,
- Ji-Hyung Park,
- Kijong Yi,
- Taewoo Kim,
- Chang Hyun Nam,
- Won Hee Lee,
- Soo A Oh,
- Yoo Jin Bae,
- Thomas M. Klompstra,
- Haeun Lee,
- Jinju Han,
- Junehwak Lee,
- Jung Woo Park,
- Jie-Hyun Kim,
- Hyunki Kim,
- Hugo Snippert,
- Bon-Kyoung Koo,
- and Young Seok Ju
Genome Res. October 2025 35: 2158-2172; Published in Advance August 26, 2025, doi:10.1101/gr.280338.124
...v2.9.2 (Kim et al. 2018) were utilized. Bulk whole- sequencing of first single-cell cloned lines, hGOiA3A, TP53KO-hGOiA3A, hGOiA3B, and TP53KO-hGOiA3B organoids, were utilized as matched normal for calling somatic mutations in doxycycline-treated organoids. False-positive variants in each call set...
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Method: Single-cell Rapid Capture Hybridization sequencing reliably detects isoform usage and coding mutations in targeted genes
- Hongke Peng,
- Jafar S. Jabbari,
- Luyi Tian,
- Changqing Wang,
- Yupei You,
- Chong Chyn Chua,
- Natasha S. Anstee,
- Noorul Amin,
- Andrew H. Wei,
- Nadia M. Davidson,
- Andrew W. Roberts,
- David C.S. Huang,
- Matthew E. Ritchie,
- and Rachel Thijssen
Genome Res. April 2025 35: 942-955; Published in Advance January 10, 2025, doi:10.1101/gr.279322.124
...by patient specificity. This emphasizes the importance of caution when drawing conclusions based on bulk RNA-seq data comparing wild-type and mutant samples from different patients.Venetoclax is an effective therapy for CLL patients with the potential to induce long remissions. However, we showed...
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Mini-Review: Large-scale genomic analysis of the domestic dog informs biological discovery
- Reuben M. Buckley and
- Elaine A. Ostrander
Genome Res. June 2024 34: 811-821; Published in Advance July 2, 2024, doi:10.1101/gr.278569.123
...drive rare variant discovery and assess the geographic distribution of canine diversity, which identifies Asia as a major source of missing variation. Finally, we review recent comparative genomic analyses that will facilitate annotation of the noncoding in dogs.The domestic dog has increasingly been...
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Method: Single-cell methylation sequencing data reveal succinct metastatic migration histories and tumor progression models
- Yuelin Liu,
- Xuan Cindy Li,
- Farid Rashidi Mehrabadi,
- Alejandro A. Schäffer,
- Drew Pratt,
- David R. Crawford,
- Salem Malikić,
- Erin K. Molloy,
- Vishaka Gopalan,
- Stephen M. Mount,
- Eytan Ruppin,
- Kenneth D. Aldape,
- and S. Cenk Sahinalp
Genome Res. July 2023 33: 1089-1100; Published in Advance June 14, 2023, doi:10.1101/gr.277608.122
....g., Brastianos et al. 2015; Gundem et al. 2015; Zhao et al. 2016). Hong et al. (2015) showed that results are sensitive to the method used for phylogeny inference. Complicating matters further is that most of the methods listed above use bulk sequencing data as input, and El-Kebir et al. (2018) showed that under...
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Method: A statistical learning method for simultaneous copy number estimation and subclone clustering with single-cell sequencing data
- Fei Qin,
- Guoshuai Cai,
- Christopher I. Amos,
- and Feifei Xiao
Genome Res. January 2024 34: 85-93; Published in Advance January 30, 2024, doi:10.1101/gr.278098.123
...Corresponding author: feifeixiao@ufl.eduAbstractThe availability of single-cell sequencing (SCS) enables us to assess intra-tumor heterogeneity and identify cellular subclones without the confounding effect of mixed cells. Copy number aberrations (CNAs) have been commonly used to identify subclones in SCS data...
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Research: Selfish mutations dysregulating RAS-MAPK signaling are pervasive in aged human testes
- Geoffrey J. Maher,
- Hannah K. Ralph,
- Zhihao Ding,
- Nils Koelling,
- Hana Mlcochova,
- Eleni Giannoulatou,
- Pawan Dhami,
- Dirk S. Paul,
- Stefan H. Stricker,
- Stephan Beck,
- Gilean McVean,
- Andrew O.M. Wilkie,
- and Anne Goriely
Genome Res. December 2018 28: 1779-1790; Published in Advance October 24, 2018, doi:10.1101/gr.239186.118
...nonsynonymous substitutions (Table 1).Several observations support the notion that the mutations identified are enriched for clonal events that are promoted by positive selection of mutant stem cells via the phenomenon of selfish spermatogonial selection. Out of the 61 validated variants (Table 1), 43...
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