Article
Cell Biology
Yang Yang, Lixing Yang
Summary: This study reveals the diversity and distinct mutational mechanisms of somatic structural variations (SVs) in pediatric brain tumors. The patterns of SVs in pediatric brain tumors are substantially different from those in adult cancers, and multiple SV signatures converge on major cancer driver genes, indicating the vital roles of somatic SVs in disease progression.
Article
Genetics & Heredity
Alejandra Damian, Gonzalo Nunez-Moreno, Claire Jubin, Alejandra Tamayo, Marta Rodriguez de Alba, Cristina Villaverde, Cedric Fund, Marc Delepine, Aurelie Leduc, Jean Francois Deleuze, Pablo Minguez, Carmen Ayuso, Marta Corton
Summary: In this study, long-read sequencing technology was used to uncover cryptic pathogenic structural variants (SVs) in two unresolved PAX6-negative cases of congenital aniridia. The study highlights the limitations of traditional short-read sequencing in detecting pathogenic SVs in low-complexity regions of the genome and demonstrates the value of long-read sequencing in identifying hidden sources of variation in rare genetic diseases.
Article
Biology
Yan Zheng, Xuequn Shang, Wing-Kin Sung
Summary: Structural variations (SVs) are genomic rearrangements larger than 50bp, and they are important in genetic diseases and evolution mechanisms. Existing long-read SV callers often fail to detect true SVs or mistakenly detect false SVs in repetitive regions and regions with multi-allelic SVs, primarily due to messy alignments caused by high error rate in ONT long reads. To address this, we propose a novel method called SVsearcher, which greatly improves SV detection accuracy and is capable of identifying a high percentage of multi-allelic SVs.
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Cheng Quan, Hao Lu, Yiming Lu, Gangqiao Zhou
Summary: Population-scale studies of structural variation are expanding rapidly with the advancement of long-read sequencing technology. The reference bias poses challenges in large-scale genotyping. Academic efforts to improve genotype quality through graphical representation of reference and alternative alleles have shown promising results in large and diverse cohorts.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Biochemical Research Methods
Tao Jiang, Shiqi Liu, Shuqi Cao, Yadong Liu, Zhe Cui, Yadong Wang, Hongzhe Guo
Summary: With the rapid development of long-read sequencing technologies, it is now possible to reveal the full spectrum of genetic structural variation (SV). However, the high cost, limited read length, and sequencing errors associated with long-read data have hindered the widespread adoption of SV calling. This study provides important guidelines for selecting long-read sequencing settings for efficient SV calling, with high sequencing coverage being the most influential factor in promoting SV calling.
BMC BIOINFORMATICS
(2021)
Article
Gastroenterology & Hepatology
Nicholas van Buuren, Ricardo Ramirez, Cameron Soulette, Vithika Suri, Dong Han, Lindsey May, Scott Turner, P. C. Parvangada, Ross Martin, Henry L. Y. Chan, Patrick Marcellin, Maria Buti, Nam Bui, Neeru Bhardwaj, Anuj Gaggar, Li Li, Hongmei Mo, Becket Feierbach
Summary: The study utilized targeted long-read sequencing to analyze HBV integration events in liver biopsies, revealing chromosomal translocation associated with HBV integration. Long-read RNA sequencing allowed for accurate quantification of HBV transcriptome, with patients showing differences in transcription origin based on HBeAg status. The findings suggest a novel mechanism with mutagenic potential that may contribute to HCC progression.
Review
Biochemical Research Methods
Jiadong Lin, Peng Jia, Songbo Wang, Walter Kosters, Kai Ye
Summary: Structural variant (SV) detection is essential for genomic studies, and comparing read-based and assembly-based strategies is important. This study investigated the factors that influence the two strategies and assessed their performance using well-curated SVs. It was found that a majority of SVs could be detected by both strategies, but discordance was mainly caused by complex SVs and inversions.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Genetics & Heredity
Yahui Gao, Li Ma, George E. Liu
Summary: Structural variations (SVs) are widely distributed in the genome and long-read sequencing outperforms short-read sequencing in detecting SVs, with PacBio CLR being the most effective in detecting large SVs.
Article
Biochemistry & Molecular Biology
Alla S. Koltsova, Olga A. Efimova, Olga V. Malysheva, Natalia S. Osinovskaya, Thomas Liehr, Ahmed Al-Rikabi, Natalia Yu. Shved, Iskender Yu. Sultanov, Olga G. Chiryaeva, Maria I. Yarmolinskaya, Nikolai I. Polenov, Vladislava V. Kunitsa, Maka I. Kakhiani, Tatyana G. Tral, Gulrukhsor Kh. Tolibova, Olesya N. Bespalova, Igor Yu. Kogan, Andrey S. Glotov, Vladislav S. Baranov, Anna A. Pendina
Summary: Uterine leiomyomas (ULs) exhibit both inter- and intratumor genetic heterogeneity. Regardless of the MED12 status, a tumor may consist of clones with and without chromosomal abnormalities. Under in vitro conditions, the clonal frequency of cells shifts up or down, possibly due to variations in the ability of cells with different genetic aberrations to survive outside the body.
Article
Biotechnology & Applied Microbiology
Nadia M. Davidson, Ying Chen, Teresa Sadras, Georgina L. Ryland, Piers Blombery, Paul G. Ekert, Jonathan Goke, Alicia Oshlack
Summary: This study presents a method, JAFFAL, for identifying fusions from long-read transcriptome sequencing. The effectiveness of JAFFAL is validated using simulations, cell lines, and patient data. Fusions spanning three genes are discovered in single-cell data using JAFFAL.
Article
Pharmacology & Pharmacy
Mingkun Guo, Shihai Li, Yifan Zhou, Menglong Li, Zhining Wen
Summary: Long-read technologies have advantages in detecting structural variations, but further exploration and comparison are needed. Three commonly used long-read SV detection pipelines show lower performance in tandem repeat regions. Comprehensive evaluation results can assist in choosing appropriate pipelines and complement the research of rare diseases.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Amy J. J. Turner, Ashley D. D. Derezinski, Andrea Gaedigk, Mark E. E. Berres, David B. B. Gregornik, Keith Brown, Ulrich Broeckel, Gunter Scharer
Summary: Complex regions in the human genome present challenges for accurate genetic analysis, particularly with short-read Next-Generation-Sequencing technologies. A PCR-free CRISPR-Cas9 based enrichment method was developed to accurately characterize the CYP2D6-CYP2D7-CYP2D8 loci, improving CYP2D6 genotyping accuracy. This method has the potential to improve clinical phenotyping and overcome testing limitations in challenging genomic regions.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemical Research Methods
Yan Zheng, Xuequn Shang
Summary: Researchers propose a new deep learning-based method, SVcnn, for detecting structural variations (SVs) using long-read sequencing data. The method outperforms other SV callers, improving F1-score by 2-8% when the read depth is greater than 5x. It also shows better performance in detecting multi-allelic SVs.
BMC BIOINFORMATICS
(2023)
Article
Multidisciplinary Sciences
Yoshitaka Sakamoto, Shuhei Miyake, Miho Oka, Akinori Kanai, Yosuke Kawai, Satoi Nagasawa, Yuichi Shiraishi, Katsushi Tokunaga, Takashi Kohno, Masahide Seki, Yutaka Suzuki, Ayako Suzuki
Summary: In this study, the authors use a combination of short and long read sequencing to analyze the chromosomal backgrounds of somatic mutations in Japanese non-small cell lung cancers. They find that certain cancer genomes exhibit regions with uneven distribution of mutations and identify large-scale chromosomal rearrangement events that are characteristic of EGFR mutation-positive lung adenocarcinomas. Additionally, the integration of long read epigenomic and transcriptomic data reveals that haploid chromosomes do not always have equivalent transcriptomic/epigenomic conditions, and distinct chromosomal backgrounds contribute to later cancerous aberrations in a haplotype-specific manner.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Sally M. Dewhurst, Xiaotong Yao, Joel Rosiene, Huasong Tian, Julie Behr, Nazario Bosco, Kaori K. Takai, Titia de Lange, Marcin Imielinski
Summary: Telomere crisis has been found to induce chromothripsis and breakage fusion bridge (BFB) cycles in vitro. This study shows that telomere crisis can generate a broader spectrum of structural variations, suggesting that cancers without chromothripsis and BFB cycles may have also originated from telomere crisis.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Ryutaro Furukawa, Shin-ichi Yokobori, Riku Sato, Taimu Kumagawa, Mizuho Nakagawa, Kazutaka Katoh, Akihiko Yamagishi
Summary: This study generated a composite phylogenetic tree for seven aminoacyl-tRNA synthetases (ARSs) and predicted the ancestral ARS sequences and amino acid specificity before the evolution of the last universal common ancestor. The results showed that the ancestral ARSs had substantial amino acid specificity and that the number of amino acid types aminoacylated by proteinaceous ARSs was limited before the appearance of a fuller range of proteinaceous ARS species.
JOURNAL OF MOLECULAR EVOLUTION
(2022)
Article
Biochemistry & Molecular Biology
Martin C. Frith
Summary: Protein fossils in genomes provide valuable insights into the ancient evolution of TEs and genomes. A recent study discovered ancient fossils in the human genome, which exhibit extreme sequence conservation and may have gene-regulatory functions.
MOLECULAR BIOLOGY AND EVOLUTION
(2022)
Article
Cell Biology
Nariko Ikemura, Shunta Taminishi, Tohru Inaba, Takao Arimori, Daisuke Motooka, Kazutaka Katoh, Yuhei Kirita, Yusuke Higuchi, Songling Li, Tatsuya Suzuki, Yumi Itoh, Yuki Ozaki, Shota Nakamura, Satoaki Matoba, Daron M. Standley, Toru Okamoto, Junichi Takagi, Atsushi Hoshino
Summary: The Omicron variant of SARS-CoV-2 has a high ability to escape neutralization by vaccines and therapeutic drugs. However, engineered ACE2 molecules can effectively neutralize Omicron and have therapeutic value against various variants.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Biochemical Research Methods
Martin C. Frith, Jim Shaw, John L. Spouge
Summary: We propose a sequence-sampling approach that optimizes sensitivity for a wide range of sequence comparison methods, particularly for randomly evolving sequences. It increases specificity for real biological DNA by avoiding simple repeats. Our approach extends the concepts of universal hitting sets and polar sets, providing insights into accurate and rapid sequence analysis.
Review
Genetics & Heredity
Eri Imagawa, Rie Seyama, Hiromi Aoi, Yuri Uchiyama, Bruno Guimaraes Marcarini, Isabel Furquim, Rachel Sayuri Honjo, Debora Romeo Bertola, Chong Ae Kim, Naomichi Matsumoto
Summary: The SUZ12, EZH2, and EED genes are essential for development and their variants have been associated with various overgrowth syndromes. The clinical manifestations of these syndromes overlap to a large extent, but their prevalence rates differ.
Article
Clinical Neurology
Maria Cristina Cioclu, Ilaria Mosca, Paolo Ambrosino, Deborah Puzo, Allan Bayat, Saskia B. Wortmann, Johannes Koch, Vincent Strehlow, Kentaro Shirai, Naomichi Matsumoto, Stephan J. Sanders, Vincent Michaud, Marine Legendre, Antonella Riva, Pasquale Striano, Hiltrud Muhle, Manuela Pendziwiat, Gaetan Lesca, Giuseppe Donato Mangano, Rosaria Nardello, Johannes R. Lemke, Rikke S. Moller, Maria Virginia Soldovieri, Guido Rubboli, Maurizio Taglialatela
Summary: This study describes the phenotypic and genetic features of patients with KCNT2-related developmental epileptic encephalopathy (DEE), and investigates the functional and pharmacological properties of KCNT2 channels carrying novel or previously untested variants. The results expand the phenotypic and genotypic spectrum of KCNT2-related disorders, and highlight the need for targeted therapies based on the molecular phenotype.
ANNALS OF NEUROLOGY
(2023)
Article
Ophthalmology
Chika Shigeyasu, Masakazu Yamada, Yohane Miyata, Yuri Uchiyama, Naomichi Matsumoto, Yumi Kusumi, Atsushi Shiraishi
Summary: The purpose of this study was to report a case of Peters plus-like syndrome that was found to have an 8q21.11 microdeletion by copy number variation analysis. A 6-month-old Japanese boy presented with bilateral corneal opacity and several facial malformations. Through copy number variation analysis using exome data and quantitative polymerase chain reaction, a de novo 4.6-Mb deletion at 8q21.11q21.13 was identified, leading to a diagnosis of 8q21.11 microdeletion syndrome.
Article
Biochemical Research Methods
Yin Yao, Martin C. C. Frith
Summary: Protein fossils, derived from transposable elements, decayed genes, and viral integrations, can provide insights into evolutionary history and relationships, but current methods for detecting them are not optimized. We present a powerful DNA-protein homology search method that is more sensitive and faster than blastx in detecting transposable element protein fossils.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2023)
Article
Clinical Neurology
Yi-Chu Liao, Cheng-Yu Wei, Fu-Pang Chang, Ying-Tsen Chou, Shao-Lun Hsu, Chih-Ping Chung, Takeshi Mizuguchi, Naomichi Matsumoto, Shaw-Fang Yet, Yi-Chung Lee
Summary: This study found that GGC repeat expansion in the NOTCH2NLC gene may contribute to cerebral small vessel disease (cSVD). A screening of 197 patients with unresolved vascular leukoencephalopathy revealed that 6 patients carried the GGC repeat expansion, and these patients exhibited clinical and neuroimaging features similar to cSVD. Therefore, the presence of NIID should be considered in patients presenting with cSVD.
Article
Genetics & Heredity
Tomoko Kobayashi, Fumiyoshi Fujishima, Kazuaki Tokodai, Chiaki Sato, Takashi Kamei, Noriko Miyake, Naomichi Matsumoto, Tomoki Kosho
Summary: Musculocontractural Ehlers-Danlos syndrome (mcEDS) is a genetic connective tissue disorder characterized by congenital malformations and fragility-related symptoms in multiple systems. Gastrointestinal complications, such as diverticula and perforation, can occur in mcEDS-CHST14 patients. We present a case of colonic perforation without diverticula in sisters with mcEDS-CHST14, successfully treated with surgery and postoperative care. It is important for teenage to 30s mcEDS-CHST14 patients experiencing abdominal pain to undergo abdominal X-ray and computed tomography.
Editorial Material
Oncology
Giovanni Pascarella, Martin Frith, Piero Carninci
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Biology
Sachiko Ohori, Akihiko Miyauchi, Hitoshi Osaka, Charles Marques Lourenco, Naohiro Arakaki, Toru Sengoku, Kazuhiro Ogata, Rachel Sayuri Honjo, Chong Ae Kim, Satomi Mitsuhashi, Martin C. Frith, Rie Seyama, Naomi Tsuchida, Yuri Uchiyama, Eriko Koshimizu, Kohei Hamanaka, Kazuharu Misawa, Satoko Miyatake, Kuniaki Saito, Takeshi Mizuguchi, Atsushi Fujita, Naomichi Matsumoto
Summary: We have identified previously undescribed biallelic single-nucleotide variants (SNVs) and structural variations (SVs) in the FGF12 gene associated with developmental and epileptic encephalopathy (DEE). These variants were detected using long-read whole genome sequencing and were confirmed to be loss-of-function through gene expression analysis and functional analysis in Drosophila. Our study demonstrates the importance of small SVs in Mendelian disorders and highlights the potential of long-read whole genome sequencing to detect these variants efficiently.
LIFE SCIENCE ALLIANCE
(2023)
Article
Genetics & Heredity
Eriko Nishi, Noriko Miyake, Rie Kawamura, Kana Hosoki, Yuiko Hasegawa, Naomichi Matsumoto, Nobuhiko Okamoto
Summary: This study investigates the occurrence and clinical significance of craniosynostosis (CS) in individuals with Kabuki syndrome (KS). The study finds that 50% of genetically diagnosed KS individuals exhibit CS, with half of them requiring cranioplasty. There are no significant differences based on sex, causative gene, and molecular consequence among individuals with KS who exhibit CS. The study also highlights that CS can be diagnosed before KS and suggests the importance of monitoring cranial deformities in KS individuals, emphasizing the use of 3DCT evaluations and digital impressions for CS concerns.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Genetics & Heredity
Keiichi Mizushima, Yuka Shibata, Shinichi Shirai, Masaaki Matsushima, Satoko Miyatake, Ikuko Iwata, Hiroaki Yaguchi, Naomichi Matsumoto, Ichiro Yabe
Summary: This study investigated the distribution of AD-SCD in Hokkaido and found that genetic analysis accurately identified the types of SCD, with a higher prevalence of SCA6 and a lower prevalence of MJD/SCA3.
JOURNAL OF HUMAN GENETICS
(2023)
Article
Medicine, General & Internal
Yusuke Noda, Jun Kido, Yohei Misumi, Keishin Sugawara, Sachiko Ohori, Atsushi Fujita, Naomichi Matsumoto, Mitsuharu Ueda, Kimitoshi Nakamura
Summary: This case report presents a child with PURA-related neurodevelopmental disorder. The child had symptoms such as microcephaly, brachygnathia, high anterior hairline, hip dysplasia, strabismus, severe hypotonia, developmental delay, feeding difficulties, and respiratory difficulties. His development ceased with age and his clinical symptoms may vary among patients with the same variant.
CLINICAL CASE REPORTS
(2023)