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Perspective: Functional genomics bridges the gap between quantitative genetics and molecular biology
- Tuuli Lappalainen
Genome Res. October 2015 25: 1427-1431; doi:10.1101/gr.190983.115
...et al. 2012), as well as translation and protein levels (Battle et al. 2015). These cellular QTL studies are enabled by continuing development of scalable and affordable molecular assays that can be applied to hundreds of samples, ideally frommultiple cell types and conditions. Other cellular QTLs...
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Perspective: The path to routine use of genomic biomarkers in the cancer clinic
- Paul C. Boutros
Genome Res. October 2015 25: 1508-1513; doi:10.1101/gr.191114.115
...and computational levels, including the problem of spatio-genomic heterogeneity in an individual cancer. I then outline the challenges in translating newly discovered genome-wide or regional events, like trinucleotide mutation signatures, kataegis, and chromothripsis, into biomarkers, as well as the importance...
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Review: Artificial intelligence and machine learning in cell-free-DNA-based diagnostics
- W.H. Adrian Tsui,
- Spencer C. Ding,
- Peiyong Jiang,
- and Y.M. Dennis Lo
Genome Res. January 2025 35: 1-19; doi:10.1101/gr.278413.123
...to challenges in methylation calling, and thus, many attempts have failed to achieve meaningful or practical accuracy for a decade (Clark et al. 2013). Tse and colleagues (2021) have developed an AI-based approach named the holistic kinetic (HK) model (Fig. 2), which takes into account the incorporation...
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Research: Transcriptomic landscape of transposable elements reveals LTR7-PLAAT4 as a potential oncogene and therapeutic target in pancreatic adenocarcinoma
- Meilong Shi,
- Chuanqi Teng,
- Shan Zhang,
- Xiaobo He,
- Lingyun Xu,
- Fengxian Han,
- Rongqi Wen,
- Ganjun Yu,
- Jingwen Liu,
- Yang Feng,
- Yanfeng Wu,
- Yan Ren,
- Gang Jin,
- and Jing Li
Genome Res. February 2026 36: 275-290; Published in Advance January 8, 2026, doi:10.1101/gr.280528.125
...contributions of transposable elements to PAAD pathogenesis and immunogenicity and to explore new opportunities for biomarker discovery and immunotherapeutic development.ResultsIntegrative analysis of transposable element activation across patient cohorts and cell line data setsTo comprehensively characterize...
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Method: ML-MAGES enables multivariate genetic association analyses with genes and effect size shrinkage
- Xiran Liu,
- Lorin Crawford,
- and Sohini Ramachandran
Genome Res. December 2025 35: 2691-2700; Published in Advance November 19, 2025, doi:10.1101/gr.280440.125
...effect estimates as well as in investigating more than one trait simultaneously. We leverage machine learning approaches for these two challenges, developing a computationally efficient method called ML-MAGES. First, we shrink the inflation in GWA effect sizes caused by nonindependence among variants...
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Perspective: Unraveling the hidden complexity of cancer through long-read sequencing
- Qiuhui Li,
- Ayse G. Keskus,
- Justin Wagner,
- Michal B. Izydorczyk,
- Winston Timp,
- Fritz J. Sedlazeck,
- Alison P. Klein,
- Justin M. Zook,
- Mikhail Kolmogorov,
- and Michael C. Schatz
Genome Res. April 2025 35: 599-620; Published in Advance March 20, 2025, doi:10.1101/gr.280041.124
...detection methods for individual samples, comprehensively profiling all SV types in a sample often requires integrating results from multiple bioinformatics algorithms. To address the challenges, several specialized SV merging tools have been developed to improve the analysis of complex genomic structures...
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Method: Harnessing agent-based frameworks in CellAgentChat to unravel cell–cell interactions from single-cell and spatial transcriptomics
- Vishvak Raghavan,
- Yumin Zheng,
- Yue Li,
- and Jun Ding
Genome Res. July 2025 35: 1646-1663; Published in Advance May 2, 2025, doi:10.1101/gr.279771.124
...sets at both single-cell (or subcellular) and spot-level resolution: Stereo-seq mouse developing hippocampus at three developmental time points (E12.5, E14.5, E16.5) (Chen et al. 2022), 10x Genomics Visium human squamous cell carcinoma (Ji et al. 2020), 10x Genomics Visium pancreatic ductal...
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Method: STCC enhances spatial domain detection through consensus clustering of spatial transcriptomics data
- Congcong Hu,
- Nana Wei,
- Jiyuan Yang,
- Hua-Jun Wu,
- and Xiaoqi Zheng
Genome Res. June 2025 35: 1415-1428; Published in Advance May 12, 2025, doi:10.1101/gr.280031.124
...Congcong Hu1, Nana Wei2,3, Jiyuan Yang1, Hua-Jun Wu2,4,5 and Xiaoqi Zheng1 1Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; 2Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education...
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Research: Analysis of a cell-free DNA–based cancer screening cohort links fragmentomic profiles, nuclease levels, and plasma DNA concentrations
- Yasine Malki,
- Guannan Kang,
- W.K. Jacky Lam,
- Qing Zhou,
- Suk Hang Cheng,
- Peter P.H. Cheung,
- Jinyue Bai,
- Ming Lok Chan,
- Chui Ting Lee,
- Wenlei Peng,
- Yiqiong Zhang,
- Wanxia Gai,
- Winsome W.S. Wong,
- Mary-Jane L. Ma,
- Wenshuo Li,
- Xinzhou Xu,
- Zhuoran Gao,
- Irene O.L. Tse,
- Huimin Shang,
- L.Y. Lois Choy,
- Peiyong Jiang,
- K.C. Allen Chan,
- and Y.M. Dennis Lo
Genome Res. January 2025 35: 31-42; Published in Advance November 27, 2024, doi:10.1101/gr.279667.124
...; 4State Key Laboratory of Translational Oncology, Sir Y.K. Pao Centre for Cancer, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China ↵5 These authors contributed equally to this work. Corresponding author: loym...
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Research: Long-read transcriptome sequencing of CLL and MDS patients uncovers molecular effects of SF3B1 mutations
- Alicja Pacholewska,
- Matthias Lienhard,
- Mirko Brüggemann,
- Heike Hänel,
- Lorina Bilalli,
- Anja Königs,
- Felix Heß,
- Kerstin Becker,
- Karl Köhrer,
- Jesko Kaiser,
- Holger Gohlke,
- Norbert Gattermann,
- Michael Hallek,
- Carmen D. Herling,
- Julian König,
- Christina Grimm,
- Ralf Herwig,
- Kathi Zarnack,
- and Michal R. Schweiger
Genome Res. November 2024 34: 1832-1848; Published in Advance September 13, 2024, doi:10.1101/gr.279327.124
...,2,14, Ralf Herwig3,14, Kathi Zarnack4,14 and Michal R. Schweiger1,2,14 1Institute for Translational Epigenetics, Faculty of Medicine, University of Cologne, 50931 Cologne, Germany; 2Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine, University of Cologne, 50931 Cologne, Germany; 3Department...
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