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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: Dynamic A-to-I RNA editing in response to gut microbiome in honey bees
- 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 gr.280291.124; Published in Advance March 4, 2026, doi:10.1101/gr.280291.124
.... 2024) supports the advantage of flexible RNA editing under 61 different biotic or abiotic conditions. Other in silico observational studies revealing such 62 flexibility include the temperature-dependent RNA editing in ectotherms (Rieder et al. 63 2015; Yablonovitch et al. 2017b; Duan et al. 2024b...
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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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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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Research: Nanopore direct RNA sequencing reveals METTL2A-mediated m³C sites in poly(A) RNA
- Shuhei Mitsutomi,
- Anzu Sugawara,
- Masahide Seki,
- Yutaka Suzuki,
- Sotaro Miyao,
- Haozhe Du,
- Kenji Takahashi,
- Yusuke Mizukami,
- Kenzui Taniue,
- and Nobuyoshi Akimitsu
Genome Res. November 2025 35: 2406-2417; Published in Advance October 30, 2025, doi:10.1101/gr.280269.124
...motif and coding sequences. METTL2A knockdown alters expression of S100A4 mRNA isoforms, which contains METTL2A-mediated m3C sites. Notably, many transcripts with METTL2A-mediated m3C sites are upregulated upon METTL2A knockdown. We reveal the transcriptome-wide presence of m3C sites in poly(A) RNA...
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Research: Long-read genomics reveal extensive nuclear-specific evolution and allele-specific expression in a dikaryotic fungus
- Rita Tam,
- Mareike Möller,
- Runpeng Luo,
- Zhenyan Luo,
- Ashley Jones,
- Sambasivam Periyannan,
- John P. Rathjen,
- and Benjamin Schwessinger
Genome Res. June 2025 35: 1364-1376; Published in Advance April 11, 2025, doi:10.1101/gr.280359.124
...replicates of each sample, with separation of samples representing dormancy (UG) and macroscopically asymptomatic (4, 6, and 8 dpi) and symptomatic (10 and 12 dpi) stages (Supplemental Fig. S6). We also complemented gene annotation with multiple publicly available Illumina RNA-seq data sets (Supplemental...
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