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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
...and treatment options. We applied long-read transcriptome sequencing (LRTS) to 44 MDS and CLL patients, as well as two pairs of isogenic cell lines with and without SF3B1 mutations, and found >60% of novel isoforms. Splicing alterations were largely shared between cancer types and specifically affected...
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Perspective: Notable challenges posed by long-read sequencing for the study of transcriptional diversity and genome annotation
- Carolina Monzó,
- Adam Frankish,
- and Ana Conesa
Genome Res. April 2025 35: 583-592; Published in Advance March 3, 2025, doi:10.1101/gr.279865.124
...annotation of transcriptome diversity. (A) Benefits and challenges of annotating the transcriptome diversity revealed by long-read sequencing methods. Challenges include storage, interpretation, and visualization of vast amounts of transcripts and are outweighed by the benefits of using a comprehensive...
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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
...years has revolutionized our ability to catalog cancer risk variants and understand the genomic landscape of cancer. Early studies relied on targeted sequencing and microarrays to detect genomic and transcriptomic variations enriched in cancer patients, revealing, for example, the prevalence...
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Method: A full-proteome, interaction-specific characterization of mutational hotspots across human cancers
- Siwei Chen,
- Yuan Liu,
- Yingying Zhang,
- Shayne D. Wierbowski,
- Steven M. Lipkin,
- Xiaomu Wei,
- and Haiyuan Yu
Genome Res. January 2022 32: 135-149; Published in Advance December 28, 2021, doi:10.1101/gr.275437.121
...-exome sequencing for tens of thousands of human cancers (Forbes et al. 2008; The International Cancer Genome et al. 2010; The Cancer Genome Atlas Research et al. 2013). Subsequent computational analyses have identified cancer driver genes in which mutations occur more frequently than expected (Futreal et al. 2004...
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Research: Diverse tumorigenic consequences of human papillomavirus integration in primary oropharyngeal cancers
- David E. Symer,
- Keiko Akagi,
- Heather M. Geiger,
- Yang Song,
- Gaiyun Li,
- Anne-Katrin Emde,
- Weihong Xiao,
- Bo Jiang,
- André Corvelo,
- Nora C. Toussaint,
- Jingfeng Li,
- Amit Agrawal,
- Enver Ozer,
- Adel K. El-Naggar,
- Zoe Du,
- Jitesh B. Shewale,
- Birgit Stache-Crain,
- Mark Zucker,
- Nicolas Robine,
- Kevin R. Coombes,
- and Maura L. Gillison
Genome Res. January 2022 32: 55-70; Published in Advance December 13, 2021, doi:10.1101/gr.275911.121
...expression is necessary but not sufficient for HPV-associated carcinogenesis. Secondary genetic events such as host gene mutations also are required (The Cancer Genome Atlas Research Network 2017; Gillison et al. 2019).HPV integration into cervical cancer s was first reported over 30 years ago (Dürst et al...
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Research: Global identification of mammalian host and nested gene pairs reveal tissue-specific transcriptional interplay
- Bertille Montibus,
- James A. Cain,
- Rocio T. Martinez-Nunez,
- and Rebecca J. Oakey
Genome Res. December 2024 34: 2163-2175; Published in Advance November 22, 2024, doi:10.1101/gr.279430.124
..., and by National Cancer Institute, National Human Genome Research Institute, National Heart, Lung, and Blood Institute, National Institute on Drug Abuse, National Institute of Mental Health, and National Institute of Neurological Disorders and Stroke. The data used for the analyses described in this manuscript...
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Method: Single-cell Rapid Capture Hybridization sequencing reliably detects isoform usage and coding mutations in targeted genes
- Hongke Peng,
- Jafar S. Jabbari,
- Luyi Tian,
- Changqing Wang,
- Yupei You,
- Chong Chyn Chua,
- Natasha S. Anstee,
- Noorul Amin,
- Andrew H. Wei,
- Nadia M. Davidson,
- Andrew W. Roberts,
- David C.S. Huang,
- Matthew E. Ritchie,
- and Rachel Thijssen
Genome Res. April 2025 35: 942-955; Published in Advance January 10, 2025, doi:10.1101/gr.279322.124
...for single-cell genomics.Single-cell sequencing technologies have revolutionized our understanding of cell state and function (Tang et al. 2009; Sandberg 2014). These approaches enable the comprehensive characterization of individual cells, revealing cancer biology and tumor heterogeneity (Stewart et al...
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Method: Accurate fusion transcript identification from long- and short-read isoform sequencing at bulk or single-cell resolution
- Qian Qin,
- Victoria Popic,
- Kirsty Wienand,
- Houlin Yu,
- Emily White,
- Akanksha Khorgade,
- Asa Shin,
- Christophe Georgescu,
- Catarina D. Campbell,
- Arthur Dondi,
- Niko Beerenwinkel,
- Francisca Vazquez,
- Aziz M. Al'Khafaji,
- and Brian J. Haas
Genome Res. April 2025 35: 967-986; Published in Advance March 14, 2025, doi:10.1101/gr.279200.124
...cell lung cancer (DMS53), and urothelial bladder cancer (RT112). Several of these cell lines are known to harbor oncogenic fusions including BCR::ABL1 in K562, TMPRSS2::ERG in VCaP, NPM1::ALK in KIJK, and FGFR3::TACC1 in RT112. We sequenced the transcriptomes of each cell line using PacBio MAS...
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Research: Extensive protein dosage compensation in aneuploid human cancers
- Klaske M. Schukken and
- Jason M. Sheltzer
Genome Res. July 2022 32: 1254-1270; Published in Advance June 14, 2022, doi:10.1101/gr.276378.121
...production of key cellular proteins. How cells adapt to and compensate for these aneuploidy-induced proteome imbalances is a key area of ongoing research.Genome-wide studies in yeast strains engineered to harbor single extra chromosomes have revealed that copy number gains result in the increased expression...
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Research: Long-read sequencing for non-small-cell lung cancer genomes
- Yoshitaka Sakamoto,
- Liu Xu,
- Masahide Seki,
- Toshiyuki T. Yokoyama,
- Masahiro Kasahara,
- Yukie Kashima,
- Akihiro Ohashi,
- Yoko Shimada,
- Noriko Motoi,
- Katsuya Tsuchihara,
- Susumu S. Kobayashi,
- Takashi Kohno,
- Yuichi Shiraishi,
- Ayako Suzuki,
- and Yutaka Suzuki
Genome Res. September 2020 30: 1243-1257; Published in Advance September 4, 2020, doi:10.1101/gr.261941.120
...) and The Cancer Genome Atlas (TCGA), have revealed causative mutations in various types of cancer (The International Cancer Genome Consortium 2010; The Cancer Genome Atlas Research Network et al. 2013). Among them, lung adenocarcinomas are one of the most well-studied cancers regarding such “cancer driver...
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