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Method: De novo antibody identification in human blood from full-length single B cell transcriptomics and matching haplotype-resolved germline assemblies
- John Beaulaurier,
- Lynn Ly,
- J. Andrew Duty,
- Carly Tyer,
- Christian Stevens,
- Chuan-Tien Hung,
- Akash Sookdeo,
- Alex W. Drong,
- Shreyas Kowdle,
- Axel Guzman-Solis,
- Domenico Tortorella,
- Daniel J. Turner,
- Sissel Juul,
- Scott Hickey,
- and Benhur Lee
Genome Res. April 2025 35: 929-941; Published in Advance March 21, 2025, doi:10.1101/gr.279392.124
...productive IGH consensus sequences, stratified by cell type. CDR3 lengths are enumerated between the junction anchor residues: Cys 104 and Try 118 (IMGT numbering) for each sequence. (D) Mutation frequency compared to the germline sequences in the FWR1–4 and CDR1–3 regions for each cell type and isotype. (E...
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Research: Lake Malawi cichlid pangenome graph reveals extensive structural variation driven by transposable elements
- Fu Xiang Quah,
- Miguel Vasconcelos Almeida,
- Moritz Blumer,
- Chengwei Ulrika Yuan,
- Bettina Fischer,
- Kirsten See,
- Ben Jackson,
- Richard Zatha,
- Bosco Rusuwa,
- George F. Turner,
- M. Emília Santos,
- Hannes Svardal,
- Martin Hemberg,
- Richard Durbin,
- and Eric Miska
Genome Res. May 2025 35: 1094-1107; Published in Advance April 10, 2025, doi:10.1101/gr.279674.124
...Lake Malawi cichlid pan graph reveals extensive structural variation driven by transposable elements Fu Xiang Quah1,2, Miguel Vasconcelos Almeida1, Moritz Blumer2, Chengwei Ulrika Yuan1,2, Bettina Fischer2, Kirsten See1, Ben Jackson2, Richard Zatha3, Bosco Rusuwa3, George F. Turner4, M. Emília...
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Research: Modest increase in the de novo single-nucleotide mutation rate in house mice born by assisted reproduction
- Laura Blanco-Berdugo,
- Alexis Garretson,
- and Beth L. Dumont
Genome Res. January 2026 36: 50-60; Published in Advance November 13, 2025, doi:10.1101/gr.281180.125
...variation rates between ART-derived and natural-born miceThe rate of de novo structural variants (SVs) is predicted to be at least one order of magnitude lower than the single-nucleotide mutation rate (Belyeu et al. 2021a), a consideration that limits our power to detect small or modest differences in SV...
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Method: Genotyping of selected germline adaptive immune system loci using short-read sequencing data
- Michael K.B. Ford,
- Ananth Hari,
- Meredith Yeager,
- Lisa Mirabello,
- Stephen Chanock,
- Ibrahim Numanagić,
- COVNET Consortium,
- and S. Cenk Sahinalp
Genome Res. September 2025 35: 2076-2086; Published in Advance August 5, 2025, doi:10.1101/gr.280314.124
...into germline immune receptor genetic variation and COVID-19, they do serve to demonstrate the utility and application of ImmunoTyper2 to disease association studies.DiscussionIG and TR loci represent some of the most repetitive regions in the human . Their inherent complexity, characterized by extensive...
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Resource: The SynMall resource for characterizing the functional impact of synonymous variation
- Chen Ye,
- Xiaoyan Li,
- Na Cheng,
- Yansen Su,
- and Junfeng Xia
Genome Res. February 2026 36: 421-431; Published in Advance December 17, 2025, doi:10.1101/gr.281257.125
...and integrates records from widely used -wide variant databases. Second, it collects extensive annotations, categorized into mutation level (describing the variant itself) and region level (describing the surrounding genomic context of the variant). Third, SynMall assembles three core modules: a customizable...
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Research: Long-read genomics reveal extensive nuclear-specific evolution and allele-specific expression in a dikaryotic fungus
- Rita Tam,
- Mareike Möller,
- Runpeng Luo,
- Zhenyan Luo,
- Ashley Jones,
- Sambasivam Periyannan,
- John P. Rathjen,
- and Benjamin Schwessinger
Genome Res. June 2025 35: 1364-1376; Published in Advance April 11, 2025, doi:10.1101/gr.280359.124
...). This is necessary to escape the plant immune system and to confer the ability to infect new host varieties.Recent progress in heterokaryotic fungi genomics, such as in arbuscular mycorrhizal fungi, has revealed extensive nuclear variations in structural and gene content (Li et al. 2019; Sperschneider et al. 2023b...
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Method: De novo detection of somatic variants in high-quality long-read single-cell RNA sequencing data
- Arthur Dondi,
- Nico Borgsmüller,
- Pedro F. Ferreira,
- Brian J. Haas,
- Francis Jacob,
- Viola Heinzelmann-Schwarz,
- Tumor Profiler Consortium,
- and Niko Beerenwinkel
Genome Res. April 2025 35: 900-913; Published in Advance March 19, 2025, doi:10.1101/gr.279281.124
...using cell mutational profiles. LongSom distinguishes somatic SNVs from noise and germline polymorphisms by applying an extensive set of hard filters and statistical tests. Applying LongSom to human ovarian cancer samples, we detected clinically relevant somatic SNVs that were validated against matched...
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Research: Genetic variation in recalcitrant repetitive regions of the Drosophila melanogaster genome
- Harsh G. Shukla,
- Mahul Chakraborty,
- and J.J. Emerson
Genome Res. September 2025 35: 2023-2040; Published in Advance July 16, 2025, doi:10.1101/gr.280728.125
...and gene conversion (Liao 1999). However, the extent of homogenization and variation in observed copy numbers may vary across tandem arrays and may be shaped by various factors (such as natural selection, drift, mutation, drive, age, size, and relative rates of different kinds of recombination) acting...
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Method: Analytical validation of germline small variant detection using long-read HiFi genome sequencing
- Nathan Hammond,
- Linda Liao,
- Pun Wai Tong,
- Zena Ng,
- Thuy-Mi P. Nguyen,
- Chandler Ho,
- Yao Yang,
- and Stuart A. Scott
Genome Res. June 2025 35: 1391-1399; Published in Advance April 11, 2025, doi:10.1101/gr.278836.123
...provide the infrastructure for long-read HiFi sequencing-based detection of germline variation, which supports the use of this innovative technology for clinical diagnostic testing.MethodsAnalytical validation specimensHigh molecular weight (HMW) reference material DNA samples were acquired from...
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Review: De novo gene birth and the conundrum of ORFan genes in bacteria
- Md. Hassan uz-Zaman and
- Howard Ochman
Genome Res. August 2025 35: 1679-1688; Published in Advance July 10, 2025, doi:10.1101/gr.280157.124
...on extensive work in eukaryotes, a “gold standard” for detection of such genes has been proposed (Vakirlis and McLysaght 2019; Zhang et al. 2019; Vakirlis et al. 2022).The gold standard of de novo gene detectionTo unambiguously establish that a gene arose de novo, the noncoding sequence that gave rise...

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