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Method: ScisTree2 enables large-scale inference of cell lineage trees and genotype calling using efficient local search
- Haotian Zhang,
- Yiming Zhang,
- Teng Gao,
- and Yufeng Wu
Genome Res. December 2025 35: 2781-2791; Published in Advance September 3, 2025, doi:10.1101/gr.280542.125
...of our knowledge, ScisTree2 is the first model-based cell lineage tree inference and genotype calling approach that is capable of handling data sets from tens of thousands of cells or more.An adult human body contains about 30 trillion cells that perform various functions. These cells are interconnected...
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Method: High-fidelity, large-scale targeted profiling of microsatellites
- Caitlin A. Loh,
- Danielle A. Shields,
- Adam Schwing,
- and Gilad D. Evrony
Genome Res. July 2024 34: 1008-1026; Published in Advance July 16, 2024, doi:10.1101/gr.278785.123
...and calculated the cost per thousand fully genotyped loci (Methods) (Supplemental Fig. S14A,B; Supplemental Note). When analyzing only the loci from our large-scale panel, our method was significantly more cost effective than WGS at all coverage levels necessary to achieve detection of Mendelian discordant loci...
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Method: Secure discovery of genetic relatives across large-scale and distributed genomic data sets
- Matthew M. Hong,
- David Froelicher,
- Ricky Magner,
- Victoria Popic,
- Bonnie Berger,
- and Hyunghoon Cho
Genome Res. September 2024 34: 1312-1323; Published in Advance August 7, 2024, doi:10.1101/gr.279057.124
...-Relate on the UK Biobank and All of Us data sets. On a data set of 200,000 individuals split between two parties, SF-Relate detects 97% of third-degree or closer relatives within 15 h of runtime. Our work enables secure identification of relatives across large-scale genomic data sets.Collaborative studies that aim...
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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
..., morphology, and disease susceptibility. We explore the limitations of current data sets for variant interpretation, tradeoffs between sequencing strategies, and the burgeoning role of long-read s for capturing structural variants. In addition, we consider how large-scale collections of whole- sequence data...
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Research: Large-scale investigation of species-specific orphan genes in the human gut microbiome elucidates their evolutionary origins
- Nikolaos Vakirlis and
- Anne Kupczok
Genome Res. June 2024 34: 888-903; Published in Advance July 8, 2024, doi:10.1101/gr.278977.124
...prediction. We build on these data, implementing further filtering steps to remove families with homology with other species, to identify putative SSOGs in the gut microbiome and to study them systematically. By looking for patterns in large-scale comparisons, we attempt to disentangle the evolutionary...
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Research: Genotype imputation from low-coverage data for medical and population genetic analyses
- Simone Andrea Biagini,
- Sara Becelaere,
- Mio Aerden,
- Tatjana Jatsenko,
- Laurens Hannes,
- Philip Van Damme,
- Jeroen Breckpot,
- Koenraad Devriendt,
- Bernard Thienpont,
- Joris Robert Vermeesch,
- Isabelle Cleynen,
- and Toomas Kivisild
Genome Res. September 2025 35: 1929-1941; Published in Advance July 22, 2025, doi:10.1101/gr.280175.124
...data sets, we introduce a filtering approach called GDI that combines genotype probability (GP), alternate allele dosage (DS), and INFO score filters. We demonstrate that the imputation tools QUILT and GLIMPSE2 achieve similar accuracy, which is high enough for broad-scale ancestry mapping...
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Method: Interpretable phenotype decoding from multicondition sequencing data with ALPINE
- Wei-Hao Lee,
- Lechuan Li,
- Ruth Dannenfelser,
- and Vicky Yao
Genome Res. December 2025 35: 2756-2769; Published in Advance October 22, 2025, doi:10.1101/gr.280566.125
...strategy to improve computational efficiency and enhance model generalizability (Methods). This approach leverages subsets of cells to update the cell embedding matrix, reducing memory usage and mitigating overfitting. This strategy is particularly valuable when processing large-scale scRNA-seq data sets...
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Method: Fast and accurate out-of-core PCA framework for large scale biobank data
- Zilong Li,
- Jonas Meisner,
- and Anders Albrechtsen
Genome Res. September 2023 33: 1599-1608; Published in Advance August 24, 2023, doi:10.1101/gr.277525.122
...://creativecommons.org/licenses/by-nc/4.0/.References ↵Abraham G, Qiu Y, Inouye M. 2017. FlashPCA2: principal component analysis of biobank-scale genotype data sets. Bioinformatics 33: 2776–2778. doi:10.1093/bioinformatics/btx299 ↵Agrawal A, Chiu AM, Le M, Halperin E, Sankararaman S. 2020. Scalable probabilistic PCA for large-scale...
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Research: Rearrangements of viral and human genomes at human papillomavirus integration events and their allele-specific impacts on cancer genome regulation
- Vanessa L. Porter,
- Michelle Ng,
- Kieran O'Neill,
- Signe MacLennan,
- Richard D. Corbett,
- Luka Culibrk,
- Zeid Hamadeh,
- Marissa Iden,
- Rachel Schmidt,
- Shirng-Wern Tsaih,
- Carolyn Nakisige,
- Martin Origa,
- Jackson Orem,
- Glenn Chang,
- Jeremy Fan,
- Ka Ming Nip,
- Vahid Akbari,
- Simon K. Chan,
- James Hopkins,
- Richard A. Moore,
- Eric Chuah,
- Karen L. Mungall,
- Andrew J. Mungall,
- Inanc Birol,
- Steven J.M. Jones,
- Janet S. Rader,
- and Marco A. Marra
Genome Res. April 2025 35: 653-670; Published in Advance December 5, 2024, doi:10.1101/gr.279041.124
..., we performed Oxford Nanopore Technologies long-read sequencing on 72 cervical cancer s from a Ugandan data set that was previously characterized using short-read sequencing. We find recurrent structural rearrangement patterns at HPV integration events, which we categorize as del(etion)-like, dup...
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Method: Proxy panels enable privacy-aware outsourcing of genotype imputation
- Degui Zhi,
- Xiaoqian Jiang,
- and Arif Harmanci
Genome Res. February 2025 35: 326-339; Published in Advance January 10, 2025, doi:10.1101/gr.278934.124
...to protect large-scale haplotype-level data sets and demonstrated their utility for outsourcing genotype imputation. Proxy panels combine mosaic haplotype generation, noise addition, locality-sensitive random hashing, and random permutations to protect against well-known linking and reidentification...
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