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Review: k-mer approaches for biodiversity genomics
- Katharine M. Jenike,
- Lucía Campos-Domínguez,
- Marilou Boddé,
- José Cerca,
- Christina N. Hodson,
- Michael C. Schatz,
- and Kamil S. Jaron
Genome Res. February 2025 35: 219-230; Published in Advance January 31, 2025, doi:10.1101/gr.279452.124
...libraries using k-mer spectraOne of the most common direct applications of k-mers in genomics is for characterization of a sequencing data set using the distribution of k-mer coverages; this is commonly referred to as k-mer spectrum or k-mer histogram. A typical k-mer spectrum of a moderately heterozygous...
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Method: k-mer manifold approximation and projection for visualizing DNA sequences
- Chengbo Fu,
- Einari A. Niskanen,
- Gong-Hong Wei,
- Zhirong Yang,
- Marta Sanvicente-García,
- Marc Güell,
- and Lu Cheng
Genome Res. May 2025 35: 1234-1246; Published in Advance April 10, 2025, doi:10.1101/gr.279458.124
...explosion by filtering k-mers that are relevant to a motif pattern. These selected k-mers are used to construct a position weight matrix (PWM) representing the motif. However, this approach typically focuses on individual motifs one at a time, failing to capture the full spectrum of patterns in the k-mer...
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Method: Seamless, rapid, and accurate analyses of outbreak genomic data using split k-mer analysis
- Romain Derelle,
- Johanna von Wachsmann,
- Tommi Mäklin,
- Joel Hellewell,
- Timothy Russell,
- Ajit Lalvani,
- Leonid Chindelevitch,
- Nicholas J. Croucher,
- Simon R. Harris,
- and John A. Lees
Genome Res. October 2024 34: 1661-1673; Published in Advance October 15, 2024, doi:10.1101/gr.279449.124
...to bacterial species in which these biases have a major effect on accuracy. The split k-mer approach does not use alignment during construction, so it is robust to diversity from a reference, either avoiding references entirely as in ska align or using the reference only as a coordinate system as in ska map...
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Method: Minimizing reference bias with an imputed personalized reference
- Kavya Vaddadi,
- Mao-Jan Lin,
- Sina Majidian,
- Taher Mun,
- and Ben Langmead
Genome Res. March 5, 2026 gr.280989.125; Published in Advance March 5, 2026, doi:10.1101/gr.280989.125
.... (Sirén et al. 2024) introduced a personalization facility to VG (Sirén et al. 2021). The method begins with an inclusive pan, then uses k-mers derived from the input reads to personalize the reference chunk-by-chunk. This has the drawbacks that (a) it requires k-mer counting over the entire input reads...
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Method: Highly accurate reference and method selection for universal cross–data set cell type annotation with CAMUS
- Qunlun Shen,
- Shuqin Zhang,
- and Shihua Zhang
Genome Res. November 2025 35: 2527-2538; Published in Advance October 1, 2025, doi:10.1101/gr.280821.125
...: zhangs@fudan.edu.cn, zsh@amss.ac.cnAbstractCell type annotation is a critical and essential task in single-cell data analysis. Various reference-based methods have provided rapid annotation for diverse single-cell data. However, selection of the optimal references and methods is often overlooked...
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Method: Long-read reconstruction of many diverse haplotypes with devider
- Jim Shaw,
- Christina Boucher,
- Yun William Yu,
- Noelle Noyes,
- and Heng Li
Genome Res. December 2025 35: 2637-2649; Published in Advance September 23, 2025, doi:10.1101/gr.280510.125
...subsequent SNP-based k-mer approach. We then realign each read using blockaligner (Liu and Steinegger 2023) against the 32 bp flanks around each filtered SNP site, replacing the site with all possible alleles and then selecting the allele that gives the highest alignment score.Finally, we encode each read...
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Research: Evolutionarily new genes in humans with disease phenotypes reveal functional enrichment patterns shaped by adaptive innovation and sexual selection
- Jian-Hai Chen,
- Patrick Landback,
- Deanna Arsala,
- Alexander Guzzetta,
- Shengqian Xia,
- Jared Atlas,
- Dylan Sosa,
- Yong E. Zhang,
- Jingqiu Cheng,
- Bairong Shen,
- and Manyuan Long
Genome Res. March 2025 35: 379-392; Published in Advance February 14, 2025, doi:10.1101/gr.279498.124
...genes owing to intensifying selective constraints over time. We propose a “pleiotropy-barrier” model that delineates higher potential for phenotypic innovation in young genes compared to older genes, a process under natural selection. Our study demonstrates that evolutionarily new genes are critical...
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Method: spRefine denoises and imputes spatial transcriptomics with a reference-free framework powered by genomic language model
- Tianyu Liu,
- Tinglin Huang,
- Wengong Jin,
- Tinyi Chu,
- Rex Ying,
- and Hongyu Zhao
Genome Res. February 3, 2026 gr.281001.125; Published in Advance February 3, 2026, doi:10.1101/gr.281001.125
...spRefine denoises and imputes spatial1 transcriptomics with a reference-free framework2 powered by genomic language model3 Tianyu Liu1,2, Tinglin Huang3, Wengong Jin4,5, Tinyi Chu2, Rex4 Ying3, Hongyu Zhao1,2*5 1Interdepartmental Program in Computational Biology &6 Bioinformatics, Yale University...
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Research: Transcriptomic and proteomic effects of gene deletion are not evolutionarily conserved
- Yang Li and
- Jianzhi Zhang
Genome Res. March 2025 35: 512-521; Published in Advance February 18, 2025, doi:10.1101/gr.280008.124
...sensitivity of these effects to the genetic background, explaining why these effects are not evolutionarily conserved. Together, our results suggest that most transcriptomic and proteomic effects of gene deletion do not inform selected-effect function. This finding has important implications for assessing and...
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Resource: CGC1, a new reference genome for Caenorhabditis elegans
- Kazuki Ichikawa,
- Massa J. Shoura,
- Karen L. Artiles,
- Dae-Eun Jeong,
- Chie Owa,
- Haruka Kobayashi,
- Yoshihiko Suzuki,
- Manami Kanamori,
- Yu Toyoshima,
- Yuichi Iino,
- Ann E. Rougvie,
- Lamia Wahba,
- Andrew Z. Fire,
- Erich M. Schwarz,
- and Shinichi Morishita
Genome Res. August 2025 35: 1902-1918; Published in Advance July 15, 2025, doi:10.1101/gr.280274.124
..., we selected CGC1, an isogenic derivative of the original reference strain N2 (Brenner 1974) by way of VC2010 (Flibotte et al. 2010). We originally called this isogenic derivative “PD1074” while calling our assembly of it “VC2010” (Yoshimura et al. 2019); however, these two names were confusingly...
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