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Method: Quantifying pathological progression from single-cell transcriptomic data with scPSS
- Samin Rahman Khan,
- M Saifur Rahman,
- M. Sohel Rahman,
- and Md Abul Hassan Samee
Genome Res. February 2026 36: 375-386; Published in Advance January 14, 2026, doi:10.1101/gr.280411.125
...are done iteratively until convergence. When we are dealing with a single cell type in scPSS, the number of clusters can be low, sometimes just one. In such cases, Harmony still performs iterative corrections to account for batch effects within that cell type.Calculating pathological shift scoresWe measure...
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Method: Deep structural clustering reveals hidden systematic biases in RNA sequencing data
- Qiang Su,
- Yi Long,
- Deming Gou,
- Junmin Quan,
- Xiaoming Zhou,
- and Qizhou Lian
Genome Res. November 2025 35: 2563-2577; Published in Advance September 19, 2025, doi:10.1101/gr.280713.125
...of high-dimensional RNA structures in determining sequencing efficiency and their impact on data quality. Our findings offer valuable insights into the underlying mechanisms of RNA structure–mediated sequencing bias. This deeper understanding enables more accurate and reliable RNA-seq analyses...
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Method: A deconvolution framework that uses single-cell sequencing plus a small benchmark data set for accurate analysis of cell type ratios in complex tissue samples
- Shuai Guo,
- Xiaoqian Liu,
- Xuesen Cheng,
- Yujie Jiang,
- Shuangxi Ji,
- Qingnan Liang,
- Andrew Koval,
- Yumei Li,
- Leah A. Owen,
- Ivana K. Kim,
- Ana Aparicio,
- Sanghoon Lee,
- Anil K. Sood,
- Scott Kopetz,
- John Paul Shen,
- John N. Weinstein,
- Margaret M. DeAngelis,
- Rui Chen,
- and Wenyi Wang
Genome Res. January 2025 35: 147-161; Published in Advance November 25, 2024, doi:10.1101/gr.278822.123
...(Newman et al. 2019) implements a batch effect correction step but offers limited improvements in deconvolving complex bulk tissues. The ensemble approach of SCDC (Dong et al. 2021) uses matched bulk and scRNA-seq data from two normal tissue samples (e.g., mouse breast) but lacks generalizability...
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Method: Tree-based differential testing using inferential uncertainty for RNA-seq
- Noor Pratap Singh,
- Euphy Y. Wu,
- Jason Fan,
- Michael I. Love,
- and Rob Patro
Genome Res. October 2025 35: 2326-2338; Published in Advance August 21, 2025, doi:10.1101/gr.279981.124
...also be explored in the future.Finally, it would be intriguing to explore the development of a TreeTerminus- and mehenDi-like approach in the context of single-cell RNA-seq analysis, where there are quite distinct but related opportunities for data-driven aggregation to increase the power...
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Method: Likelihood-based deconvolution of bulk gene expression data using single-cell references
- Dan D. Erdmann-Pham,
- Jonathan Fischer,
- Justin Hong,
- and Yun S. Song
Genome Res. October 2021 31: 1794-1806; Published in Advance July 22, 2021, doi:10.1101/gr.272344.120
...the effectiveness of our method, called RNA-Sieve, across a diverse array of scenarios involving real data and discuss extensions made uniquely possible by our probabilistic framework, including a demonstration of well-calibrated confidence intervals.Bulk RNA sequencing (RNA-seq) has proven a useful tool...
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Research: Intergenic accumulation of RNA polymerase II maintains the potential for swift transcriptional restart upon release from quiescence
- Manuela Baquero Pérez,
- Gertjan Laenen,
- Isabelle Loïodice,
- Mickaël Garnier,
- Ugo Szachnowski,
- Antonin Morillon,
- Myriam Ruault,
- and Angela Taddei
Genome Res. October 2025 35: 2226-2239; Published in Advance August 12, 2025, doi:10.1101/gr.279874.124
..., as monitored by single-cell RNA-seq. Our results point toward a role for quiescent-specific RNAPII distribution to ensure a rapid and robust transcriptional response upon return to growth.Eukaryotic organization is dynamic, varying across cell types and conditions, both functionally and spatially...
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Research: Low-frequency somatic copy number alterations in normal human lymphocytes revealed by large-scale single-cell whole-genome profiling
- Lu Liu,
- He Chen,
- Cheng Sun,
- Jianyun Zhang,
- Juncheng Wang,
- Meijie Du,
- Jie Li,
- Lin Di,
- Jie Shen,
- Shuang Geng,
- Yuhong Pang,
- Yingying Luo,
- Chen Wu,
- Yusi Fu,
- Zhe Zheng,
- Jianbin Wang,
- and Yanyi Huang
Genome Res. January 2022 32: 44-54; Published in Advance December 28, 2021, doi:10.1101/gr.275453.121
.... We then applied our percentage classification method to identify the Chr Y copy number for each single cell.Data accessThe whole- and RNA-seq data generated in this study have been submitted to the Genome Sequence Archive (GSA; https://ngdc.cncb.ac.cn/gsa-human) in the National Genomics Data Center...
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Method: BayesRVAT enhances rare-variant association testing through Bayesian aggregation of functional annotations
- Antonio Nappi,
- Liubov Shilova,
- Theofanis Karaletsos,
- Na Cai,
- and Francesco Paolo Casale
Genome Res. December 2025 35: 2682-2690; Published in Advance October 24, 2025, doi:10.1101/gr.280689.125
...- sequencing studies. Nat Methods 19: 1599–1611. doi:10.1038/s41592-022-01640-x ↵Li T, Zhang Y, Patil P, Johnson WE. 2023. Overcoming the impacts of two-step batch effect correction on gene expression estimation and inference. Biostatistics 24: 635–652. doi:10.1093/biostatistics/kxab039 ↵Linder J, Srivastava D...
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Method: A generic, cost-effective, and scalable cell lineage analysis platform
- Tamir Biezuner,
- Adam Spiro,
- Ofir Raz,
- Shiran Amir,
- Lilach Milo,
- Rivka Adar,
- Noa Chapal-Ilani,
- Veronika Berman,
- Yael Fried,
- Elena Ainbinder,
- Galit Cohen,
- Haim M. Barr,
- Ruth Halaban,
- and Ehud Shapiro
Genome Res. November 2016 26: 1588-1599; Published in Advance August 24, 2016, doi:10.1101/gr.202903.115
..., such as expression data derived from protocols that extract both DNA and RNA of the same SC (Dey et al. 2015; Macaulay et al. 2015). A detailed description of the computational analysis pipelines is provided in Supplemental Note S3, Supplemental Figures S7–S12, and Supplemental Table S4. Cell lineage tree of ex vivo...
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Research: Degrees of convergent evolution in rodent adaptations to arid environments
- Domitille Chalopin,
- Carine Rey,
- Jeremy Ganofsky,
- Juliana Blin,
- Pascale Chevret,
- Marion Mouginot,
- Laurent Guéguen,
- Bastien Boussau,
- Sophie Pantalacci,
- and Marie Sémon
Genome Res. March 2026 36: 472-486; Published in Advance January 21, 2026, doi:10.1101/gr.280089.124
...33 and 11 species, respectively (Figs. 2, 3A,E). Not all species for which RNA-seq data were available were selected for these data sets, as the selection needed to balance the many requirements for gene expression analysis (reproducible kidney dissection, RNA quality and batch effect, number...
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