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Method: Analysis of coding gene expression from small RNA sequencing
- Aygun Azadova,
- Anthonia Ekperuoh,
- Greg N. Brooke,
- and Antonio Marco
Genome Res. March 2026 36: 611-618; Published in Advance February 10, 2026, doi:10.1101/gr.281364.125
...genomics. Early works in molecular biology on gene expression were limited, because purified RNA is unstable and difficult to work with. However, the discovery (and use in the laboratory) of reverse transcriptase, permitting the controlled synthesis of RNAs into cDNAs (Maniatis et al. 1976...
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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
...Biosciences). After clonal expansion, genomic DNA was extracted from each clone using the SimplePrep reagent for DNA (Takara, #9180) and screened for mutations by quantitative PCR (qPCR). Candidate clones were further verified for mutations by Sanger sequencing.RNA interferenceSmall interfering RNA (siRNA...
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Method: Long-read RNA sequencing reveals allele-specific N⁶-methyladenosine modifications
- Dayea Park and
- Can Cenik
Genome Res. April 2025 35: 999-1011; Published in Advance October 29, 2024, doi:10.1101/gr.279270.124
...as only one allele is expressed. Allele-specific DNA methylation and chromatin composition are two well-established epigenetic systems that control imprinted gene expression (Fournier et al. 2002; Singh et al. 2010; Prendergast et al. 2012).ASE can reflect differential rates of transcription, mRNA...
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Research: Genetic regulation of nascent RNA maturation revealed by direct RNA nanopore sequencing
- Karine Choquet,
- Louis-Philippe Chaumont,
- Simon Bache,
- Autum R. Baxter-Koenigs,
- and L. Stirling Churchman
Genome Res. April 2025 35: 712-724; Published in Advance February 14, 2025, doi:10.1101/gr.279203.124
...peptides to the immune system (Voorter et al. 2016), it is critical to understand how polymorphisms impact HLA pre-mRNA maturation. However, due to the technical challenges associated with analyzing HLA transcripts using short-read RNA-seq reads, HLA genetic variation has been primarily studied at the DNA...
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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
...and is expected to improve the interpretation of transcriptomic data in future genomic studies.RNA sequencing (RNA-seq) has become an essential tool for characterizing transcriptomes (Stark et al. 2019), enabling comprehensive profiling of gene expression, including tissue-specific patterns, disease...
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Method: Autoencoders for genomic variation analysis
- Margarita Geleta,
- Daniel Mas Montserrat,
- Xavier Giro-i-Nieto,
- and Alexander G. Ioannidis
Genome Res. February 2026 36: 348-360; Published in Advance January 20, 2026, doi:10.1101/gr.280086.124
...“logistic mixing,” a neural network without hidden layers that uses a simple update rule to adjust the output probabilities for better bitstream coding. This idea has been brought to genomic compression of sequencing reads with GeCo3 (Silva et al. 2020). Another recent use of neural networks for DNA...
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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
...K, Ooka H, Yamamoto M, Suzuki K, Kawai J, Carninci P, Ohtomo Y, Murakami K, et al. 2003. Antisense transcripts with rice full-length cDNAs. Genome Biol 5: R5. Ozsolak F, Milos PM. 2011. RNA sequencing: advances, challenges and opportunities. Nat Rev Genet 12: 87–98. Peisley A, Jo MH, Lin C, Wu B...
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Resource: MPRAbase a Massively Parallel Reporter Assay database
- Jingjing Zhao,
- Fotis A Baltoumas,
- Maxwell A Konnaris,
- Ioannis Mouratidis,
- Zhe Liu,
- Jasmine Sims,
- Vikram Agarwal,
- Georgios A Pavlopoulos,
- Ilias Georgakopoulos-Soares,
- and Nadav Ahituv
Genome Res. April 22, 2025 gr.280387.124; Published in Advance April 22, 2025, doi:10.1101/gr.280387.124
...-by-one testing limitation of these classic reporter assays, MPRAs add a DNA barcode that is transcribed if the sequence has regulatory activity and can be measured via RNA-sequencing (RNA-seq), providing a way to examine the functional effects of thousands of sequences in parallel (Patwardhan et al. 2009; Inoue...
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Method: Nanopore-based consensus sequencing enables accurate multimodal tumor cell-free DNA profiling
- Li-Ting Chen,
- Myrthe Jager,
- Dàmi Rebergen,
- Geertruid J. Brink,
- Tom van den Ende,
- Willem Vanderlinden,
- Pauline Kolbeck,
- Marc Pagès-Gallego,
- Ymke van der Pol,
- Nicolle Besselink,
- Norbert Moldovan,
- Nizar Hami,
- Wigard P. Kloosterman,
- Hanneke van Laarhoven,
- Florent Mouliere,
- Ronald Zweemer,
- Jan Lipfert,
- Sarah Derks,
- Alessio Marcozzi,
- and Jeroen de Ridder
Genome Res. April 2025 35: 886-899; Published in Advance January 13, 2025, doi:10.1101/gr.279144.124
...number alterations (CNAs), which occur in more than 90% of solid tumors (Hieronymus et al. 2018; Hoadley et al. 2018; Steele et al. 2022; Martínez-Jiménez et al. 2023). In addition to traditional genomic mutation features, -wide cfDNA sequencing also enables the detection of so-called fragmentomics...
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Method: De novo detection of somatic variants in high-quality long-read single-cell RNA sequencing data
- Arthur Dondi,
- Nico Borgsmüller,
- Pedro F. Ferreira,
- Brian J. Haas,
- Francis Jacob,
- Viola Heinzelmann-Schwarz,
- Tumor Profiler Consortium,
- and Niko Beerenwinkel
Genome Res. April 2025 35: 900-913; Published in Advance March 19, 2025, doi:10.1101/gr.279281.124
...al. 2023). While those reads are removed from transcript counts, they are valuable to call SNVs in scRNA-seq (as they come from same-cell DNA) and they can explain the large fraction of intronic variants we observed. A whole- sequencing (WGS) study of a cohort of 962 individuals (Morrison et al. 2013...
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