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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
...-in sequences reveals 16 major clusters among the 65,536 spike-ins. (D,E) Visualization of all spike-in RNAs, color-coded by GC-content cluster and by MFE cluster. The nine GC-content categories and 120 MFE levels reflect the full breadth of the 65,536 spike-in sequences.For validation, we designed synthetic...
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Method: Global mapping of RNA homodimers in living cells
- Marta M. Gabryelska,
- Andrew P. Badrock,
- Jian You Lau,
- Raymond T. O'Keefe,
- Yanick J. Crow,
- and Grzegorz Kudla
Genome Res. May 2022 32: 956-967; Published in Advance March 24, 2022, doi:10.1101/gr.275900.121
..., understanding RNA dimerization has been hampered by the lack of systematic in vivo detection methods. Here, we show that CLASH, PARIS, and other RNA proximity ligation methods detect RNA homodimers transcriptome-wide as “overlapping” chimeric reads that contain more than one copy of the same sequence. Analyzing...
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Method: Robust 16S rRNA classification based on a compressed LCA index
- Omar Ahmed,
- Christina Boucher,
- and Ben Langmead
Genome Res. December 2025 35: 2650-2660; Published in Advance August 25, 2025, doi:10.1101/gr.279846.124
...in expectation under a random model we propose here. We implemented these ideas in an open-source tool called Cliffy that performs efficient taxonomic classification of sequencing reads with respect to a compressed taxonomic index. When applied to simulated 16S rRNA reads, Cliffy's read-level accuracy is higher...
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Research: Dynamics and consequences of differential RNA isoform production during cardiomyocyte fate determination and early-stage maturation
- Joanna Delimata-Raczek,
- Natalia Koralewska,
- Bart Krist,
- Magdalena Rakoczy,
- Marek Figlerowicz,
- and Ireneusz Stolarek
Genome Res. April 3, 2026 gr.281150.125; Published in Advance April 3, 2026, doi:10.1101/gr.281150.125
...stage transition (258 in D0/D2, 36 in D2/D4, and 484 in D4/D30). A Fisher's exact test revealed 91 that DTA was not randomly distributed; instead, it was significantly overrepresented in protein-92 coding, retained intron, and lncRNA transcripts (P < 0.01). 93 To experimentally validate...
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Research: Genome-wide nucleosome and transcription factor responses to genetic perturbations reveal chromatin-mediated mechanisms of transcriptional regulation
- Kevin Moyung,
- Yulong Li,
- Heather K. MacAlpine,
- Alexander J. Hartemink,
- and David M. MacAlpine
Genome Res. January 2026 36: 115-128; Published in Advance December 9, 2025, doi:10.1101/gr.279637.124
...typically exhibit promoter regions in which nucleosomes have been evicted or shifted out to allow TFs to bind, as well as gene bodies in which nucleosomes have been disrupted by the passage of RNA polymerase (Jiang and Pugh 2009).We analyzed the features of chromatin structure that differed among...
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Resource: Isoform- and pathway-specific regulation of post-transcriptional RNA processing in human cells
- Ishwarya Venkata Narayanan,
- Karan Bedi,
- Brian Magnuson,
- Ariel McShane,
- Mario Ashaka,
- Michelle Paulsen,
- Thomas E Wilson,
- and Mats Ljungman
Genome Res. March 26, 2026 gr.280892.125; Published in Advance March 26, 2026, doi:10.1101/gr.280892.125
...were generally stronger at the 2h chase than at the 6h chase period, and 201 that the grouping of cell lines based on RNA stability values for 17,049 genes, as 202 revealed by hierarchical clustering, largely differed between the two chase periods (Fig. 203 2A,B). 204 10 To assess whether turnover...
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Research: Dynamic A-to-I RNA editing in response to gut microbiome in honeybees
- Yuange Duan,
- Min Huang,
- Lin Ye,
- Ling Ma,
- Yashuai Wu,
- Yating Du,
- Jiyao Liu,
- Fan Song,
- Li Tian,
- Wanzhi Cai,
- Hu Li,
- Xin Zhou,
- and Shiqi Luo
Genome Res. March 4, 2026 ; Published in Advance March 4, 2026, doi:10.1101/gr.280291.124
...in which CV samples exhibited greater molecular variation compared with GF samples. Principal component analysis (PCA) based on both gene expression and RNA editing levels revealed that CV sampleswerewidely dispersed, whereas GF samples formed a tightly clustered group (Fig. 3A), suggesting greater...
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Research: Transcriptome-wide systematic search does not detect A-to-I RNA editing in cis-antisense RNA duplexes
- Zohar Rosenwasser,
- Roni Cohen-Fultheim,
- Ofir Shliefer,
- Erez Y. Levanon,
- and Eli Eisenberg
Genome Res. March 12, 2026 gr.280820.125; Published in Advance March 12, 2026, doi:10.1101/gr.280820.125
...are rare, and thus this method allows determining the edited strand even for unstranded RNA-seq data: A-to-G clusters attest for editing on the positive strand, while T-to-C clusters (as observed when mapping the reads to the positive strand, i.e. the reference sequence) attest for editing of an RNA...
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Method: Kernel-bounded clustering for spatial transcriptomics enables scalable discovery of complex spatial domains
- Hang Zhang,
- Yi Zhang,
- Kai Ming Ting,
- Jie Zhang,
- and Qiuran Zhao
Genome Res. February 2025 35: 355-367; Published in Advance February 5, 2025, doi:10.1101/gr.278983.124
...the Weisfeiler–Lehman scheme (WL) (Shervashidze et al. 2011). Our ablation studies reveal that (1) KBC is the best clustering algorithm compared with existing clustering algorithms, and (2) although the WL scheme is the second-best method in terms of the clustering performance compared with SpatialPCA (Shang...
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Research: Contiguous and complete assemblies of Blastocystis gut microbiome–associated protists reveal evolutionary diversification to host ecology
- Abigail L. Lind,
- Nathan A. McDonald,
- Elias R. Gerrick,
- Ami S. Bhatt,
- and Katherine S. Pollard
Genome Res. June 2025 35: 1377-1390; Published in Advance April 22, 2025, doi:10.1101/gr.279080.124
...-read, short-read, and Hi-C DNA sequencing, alongside gene annotation and RNA sequencing. Comparative genomic analyses reveal significant variation in gene content and structure across Blastocystis. Notably, three strains from herbivorous tortoises, phylogenetically distant from human subtypes, have markedly...
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