Article
Genetics & Heredity
Souvik Seal, Abhirup Datta, Saonli Basu
Summary: This paper introduces a new method called PredLMM for estimating heritability in large-scale cohort studies. The method has better computational complexity and provides a fast alternative. Extensive simulation studies and application to the UK Biobank cohort demonstrate the accuracy and robustness of the method.
Article
Multidisciplinary Sciences
Stephen A. Schlebusch, Jakub Ridl, Manon Poignet, Francisco J. Ruiz-Ruano, Jiri Reif, Petr Pajer, Jan Paces, Tomas Albrecht, Alexander Suh, Radka Reifova
Summary: The germline-restricted chromosome (GRC) in songbirds is an extra chromosome with unknown function found only in their germline. This study examines and compares the GRC in two closely related nightingale species, revealing significant genetic differences and only one conserved gene with probable essential function. Despite its apparent indispensability, the genetic composition, function, and evolutionary significance of the GRC are still poorly understood.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Jian Sang, Tongwu Zhang, Jung Kim, Mengying Li, Angela C. Pesatori, Dario Consonni, Lei Song, Jia Liu, Wei Zhao, Phuc H. Hoang, Dave S. Campbell, James Feng, Monica E. D'Arcy, Naoise Synnott, Yingxi Chen, Zeni Wu, Bin Zhu, Xiaohong R. Yang, Kevin M. Brown, Jiyeon Choi, Jianxin Shi, Maria Teresa Landi
Summary: A new rare deleterious variant (RDV) and two previously reported RDVs were found to be associated with lung cancer risk. Additionally, new candidate susceptibility genes were identified, and enrichment of RDVs in homologous recombination repair and Fanconi anemia pathways was observed in lung cancer cases. These findings improve our understanding of lung cancer heritability and may contribute to risk stratification and prevention strategies.
HUMAN MOLECULAR GENETICS
(2022)
Article
Computer Science, Information Systems
Javier E. Soto, Paulo Ubisse, Yaime Fernandez, Cecilia Hernandez, Miguel Figueroa
Summary: The paper introduces a method and hardware accelerator to approximate the empirical entropy of a large data set with high throughput and sublinear memory requirements. It uses streaming algorithms and sketches to compute the cardinality of the stream and the frequencies of the top-K elements, estimating the contribution to entropy of the rest of the stream assuming a simple uniform distribution. Implemented on a Xilinx UltraScale+ ZCU102 FPGA, the accelerator achieves less than 1.5% mean relative error in estimating empirical entropy with a latency of 21 microseconds and a minimum throughput of 204 gigabits per second.
Article
Multidisciplinary Sciences
Martin A. M. Reijns, David A. Parry, Thomas C. Williams, Ferran Nadeu, Rebecca L. Hindshaw, Diana O. Rios Szwed, Michael D. Nicholson, Paula Carroll, Shelagh Boyle, Romina Royo, Alex J. Cornish, Hang Xiang, Kate Ridout, Anna Schuh, Konrad Aden, Claire Palles, Elias Campo, Tatjana Stankovic, Martin S. Taylor, Andrew P. Jackson
Summary: Transcription-associated mutagenesis plays an important role in human genome mutations. This study reveals an ID4 mutation signature associated with the activity of topoisomerase 1 (TOP1), which causes insertions and deletions in cancer and physiological settings.
Article
Biochemical Research Methods
Duran Zhao, Johanna L. Jones, Robert J. Gasperini, Jac C. Charlesworth, Guei-Sheung Liu, Kathryn P. Burdon
Summary: Identification of genes causing cataract is crucial for understanding the pathology of inherited pediatric cataract and developing new therapies. This study presents a step-by-step pipeline to evaluate cataract candidate genes in zebrafish using CRISPR-Cas9, offering a simple and efficient method for assessment in basic laboratory settings.
Article
Immunology
Rosalyn W. Sayaman, Mohamad Saad, Vesteinn Thorsson, Donglei Hu, Wouter Hendrickx, Jessica Roelands, Eduard Porta-Pardo, Younes Mokrab, Farshad Farshidfar, Tomas Kirchhoff, Randy F. Sweis, Oliver F. Bathe, Carolina Heimann, Michael J. Campbell, Cynthia Stretch, Scott Huntsman, Rebecca E. Graff, Najeeb Syed, Laszlo Radvanyi, Simon Shelley, Denise Wolf, Francesco M. Marincola, Michele Ceccarelli, Jerome Galon, Elad Ziv, Davide Bedognetti
Summary: Understanding the host's genetic background's contribution to cancer immunity has significant impact on the composition and functional orientation of the tumor immune microenvironment, with certain genes potentially acting as immune modulators. Investigating the effects of germline variants on immune traits provides a resource toward further understanding tumor-immune interactions.
Article
Multidisciplinary Sciences
Dimitrios Vitsios, Ryan S. Dhindsa, Dorota Matelska, Jonathan Mitchell, Xuequing Zou, Joshua Armenia, Fengyuan Hu, Quanli Wang, Ben Sidders, Andrew R. Harper, Slave Petrovski
Summary: Large reference datasets have allowed us to determine germline genetic variation intolerance in genes and genic subregions. We introduced a new metric, OncMTR, which identified genic subregions enriched with cancer-driving mutations that are depleted of germline variation. OncMTR significantly predicted driver mutations in hematologic malignancies and improved genetic signals for these diseases.
Article
Multidisciplinary Sciences
Richard Barfield, Conghui Qu, Robert S. Steinfelder, Chenjie Zeng, Tabitha A. Harrison, Stefanie Brezina, Daniel D. Buchanan, Peter T. Campbell, Graham Casey, Steven Gallinger, Marios Giannakis, Stephen B. Gruber, Andrea Gsur, Li Hsu, Jeroen R. Huyghe, Victor Moreno, Polly A. Newcomb, Shuji Ogino, Amanda I. Phipps, Martha L. Slattery, Stephen N. Thibodeau, Quang M. Trinh, Amanda E. Toland, Thomas J. Hudson, Wei Sun, Syed H. Zaidi, Ulrike Peters
Summary: This study assessed the associations between germline variations and somatic events in colorectal cancer (CRC) through two complementary approaches. The analysis revealed that a germline variant located within a CNV region associated with TLR3 was also associated with a non-silent mutation within the FBXW7 gene. Additionally, a germline variant located in the CDX1/PDGFRB gene frequently gained/lost in colorectal tumors was found to be associated with overall CRC risk.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Kez Cleal, Duncan M. Baird
Summary: Structural variation (SV) is important in genome evolution and disease, and Dysgu is a tool that accurately detects SVs using paired-end or long-read sequencing, with high sensitivity and fast running speed.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Oncology
Lizhen Zhu, Beiping Miao, Dagmara Dymerska, Magdalena Kuswik, Elena Bueno-Martinez, Lara Sanoguera-Miralles, Eladio A. Velasco, Nagarajan Paramasivam, Matthias Schlesner, Abhishek Kumar, Ying Yuan, Jan Lubinski, Obul Reddy Bandapalli, Kari Hemminki, Asta Foersti
Summary: Whole-genome sequencing and functional characterization studies on colorectal cancer families identified CYBA and TRPM4 as candidate predisposition genes that mechanistically involve intestinal barrier integrity through reactive oxygen species and mucus biology, converging in chronic bowel inflammation, a known risk factor for colorectal cancer.
Article
Multidisciplinary Sciences
Hui Li, Rahul Mazumder, Xihong Lin
Summary: This study introduces a new method called HEELS for local heritability estimation, which significantly improves the statistical efficiency of summary-statistics-based heritability estimator. The study also proposes an LD approximation strategy that reduces storage and memory costs and improves the computational efficiency of heritability estimation.
NATURE COMMUNICATIONS
(2023)
Article
Public, Environmental & Occupational Health
Christine E. Napier, Grace Davies, Phyllis N. Butow, Timothy E. Schlub, Megan C. Best, Nicci Bartley, Ilona Juraskova, Bettina Meiser, Katherine M. Tucker, Barbara B. Biesecker, David M. Thomas, Mandy L. Ballinger
Summary: Germline genome sequencing (GS) is important in cancer diagnosis and risk management. This study explores the knowledge and behavioral change intentions of individuals and their relatives regarding GS. The results show that increasing GS knowledge and targeting specific populations can lead to improved cancer outcomes.
PATIENT EDUCATION AND COUNSELING
(2022)
Article
Multidisciplinary Sciences
Hafdis T. Helgadottir, Jessada Thutkawkorapin, Kristina Lagerstedt-Robinson, Annika Lindblom
Summary: Identifying pathogenic variants in individuals with a strong family history of breast cancer remains challenging, despite advancements in sequencing technology. Through exome sequencing, known pathogenic variants in BRIP1 and PALB2 genes were identified, along with 22 high-risk variants in novel breast cancer candidate genes. Further studies are needed to validate these findings and explore the potential roles of these genes in breast cancer susceptibility.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Jung Hun Oh, Sangkyu Lee, Maria Thor, Barry S. Rosenstein, Allen Tannenbaum, Sarah Kerns, Joseph O. Deasy
Summary: This study used a machine learning-based modeling method to assess the risk of radiation-induced hematuria in prostate cancer patients using genome-wide common single nucleotide polymorphisms (SNPs). The results showed that this method can effectively stratify patients into high and low risk groups and identified key proteins and biological processes associated with the risk of hematuria.
RADIOTHERAPY AND ONCOLOGY
(2023)