December 1, 2025 – This month Genome Research (https://genome.org) publishes a special issue highlighting novel advances in computational biology.
In collaboration with the 29th International Conference on Research in Computational Molecular Biology (RECOMB), Genome Research publishes a collection of novel computational methods and their applications in genomics, including single-cell and spatial transcriptomics. These include algorithmic innovations in haplotype assembly and phasing, the analysis of genomic variation and its association to phenotype, and metagenomic data analyses. Several of these studies are highlighted below.
LLOKI (Haber et al. 2025) is a method for integrating image-based spatial transcriptomics data across multiple platforms by incorporating feature alignment across gene panels and batch alignment across technologies. When tested on real data, LLOKI outperforms existing methods at identifying spatial gene programs in normal physiology and disease.
Chandra et al. (2025) present a method, Pangenome-based Haplotype Inference (PHI), that uses pangenome references to improve genotyping accuracy from short-read sequencing data. When tested on a sample dataset of haploid genomes, this method accurately estimates haplotype sequences in low-coverage inputs and repeat-rich regions.
Methods that aim to improve metagenomic analyses are also presented. Shaw et al. (2025) present devider, a method for haplotyping small sequences from long-read sequencing data including in heterogeneous mixtures like viral coinfection and metagenomes.
Long-read approaches like optical genome mapping (OGM) offer an accurate approach for measuring large structural variations. OMKar (Raeisi Dehkordi et al. 2025) generates virtual karyotypes from OGM data to robustly detect constitutional genetic abnormalities.
This partnership between RECOMB and Genome Research brings novel computational methodologies to a broader genomics audience. Additional cutting-edge computational methods that advance studies across genome biology are also included in this Special Issue.
Interested reporters may obtain copies of the manuscript via email from Tara Bonet-Black, Administrative Assistant, Genome Research (bonetbl@cshl.edu).
About the articles:
Ahmed O, Boucher C, Langmead B. 2025. Robust 16S rRNA classification based on a compressed LCA index. Genome Research doi:10.1101/gr.279846.124
Al-Abri R, Gürsoy G. 2025. Estimating the size of long tandem repeat expansions from short reads with ScatTR. Genome Research doi:10.1101/gr.280563.125
Battistella E, Maheshwari A, Ekim B, Berger B, Popic V. 2025. Graph-based deep reinforcement learning for haplotype assembly with Ralphi. Genome Research doi:10.1101/gr.280569.125
Borozan B, Prusina T, Borozan L, Ševerdija D, Rojas Ringeling F, MatijevićD, Canzar S. 2025. Optimal marker genes for c-separated cell types with SepSolve. Genome Research doi:10.1101/gr.280637.125
Chandra G, Hossen MH, Scholz S, Dilthey AT, Gibney D, Jain C. 2025. Pangenome-based genome inference using integer programming. Genome Research. doi:10.1101/gr.280567.125
Dokmai N, Zhu K, Sahinalp SC, Cho H. 2025. Secure phasing of private genomes in a trusted execution environment with TX-Phase. Genome Research. doi:10.1101/gr.280558.125
Haber E, Deshpande A, Ma J, Krieger S. 2025. Unified integration of spatial transcriptomics across platforms with LLOKI. Genome Research. doi:10.1101/gr.280803.125
Lee W-H, Li L, Dannenfelser R, Yao V. 2025. Interpretable phenotype decoding from multicondition sequencing data with ALPINE. Genome Research. doi:10.1101/gr.280566.125
Liu X, Crawford L, Ramachandran S. 2025. ML-MAGES enables multivariate genetic association analyses with genes and effect size shrinkage. Genome Research.. doi:10.1101/gr.280440.125
Nappi A, Shilova L, Karaletsos T, Cai N, Casale FP. 2025. BayesRVAT enhances rare-variant association testing through Bayesian aggregation of functional annotations. Genome Research. doi:10.1101/gr.280689.125
Raeisi Dehkordi S, Jia Z, Estabrook J, Hauenstein J, Miller N, Güleray-Lafci N, Neesen J, Hastie A, Chaubey A, Wing Chun Pang A, et al. 2025. OMKar automates genome karyotyping using optical maps to identify constitutional abnormalities. Genome Research. doi:10.1101/gr.280536.125
Shaw J, Boucher C, YuYW, Noyes N, Li H. 2025. Long-read reconstruction of many diverse haplotypes with devider. Genome Research. doi:10.1101/gr.280510.125
Song Z, Zahin T, Li X, Shao M. 2025. Accurate detection of tandem repeats from error-prone sequences with EquiRep. Genome Research. doi:10.1101/gr.280750.125
Wang A, Hicks S, Geman D, Younes L. 2025. Label-free selection of marker genes in single-cell and spatial transcriptomics with geneCover. Genome Research. doi:10.1101/gr.280539.125
Zhang H, Zhang Y, Gao T, Wu Y. 2025. ScisTree2 enables large-scale inference of cell lineage trees and genotype calling using efficient local search. Genome Research. doi:10.1101/gr.280542.125
Zheng H, Sarkar H, Raphael BJ. 2025. Joint imputation and deconvolution of gene expression across spatial transcriptomics platforms. Genome Research. doi:10.1101/gr.280555.125
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About Genome Research:
Launched in 1995, Genome Research (www.genome.org) is an international, continuously published, peer-reviewed journal that focuses on research that provides novel insights into the genome biology of all organisms, including advances in genomic medicine. Among the topics considered by the journal are genome structure and function, comparative genomics, molecular evolution, genome-scale quantitative and population genetics, proteomics, epigenomics, and systems biology. The journal also features exciting gene discoveries and reports of cutting-edge computational biology and high-throughput methodologies.
About Cold Spring Harbor Laboratory Press:
Cold Spring Harbor Laboratory Press is an internationally renowned publisher of books, journals, and electronic media, located on Long Island, New York. Since 1933, it has furthered the advance and spread of scientific knowledge in all areas of genetics and molecular biology, including cancer biology, plant science, bioinformatics, and neurobiology. The Press is a division of Cold Spring Harbor Laboratory, an innovator in life science research and the education of scientists, students, and the public. For more information, visit our website at http://cshlpress.org.
Genome Research issues press releases to highlight significant research studies that are published in the journal.
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