Article
Biochemical Research Methods
Juan A. Ferrer-Bonsoms, Laura Jareno, Angel Rubio
Summary: Rediscover is a software package for identifying mutually exclusive genomic events, offering both exact and approximate computations of the PB. Compared to Discover, Rediscover is slightly faster for large and medium-sized datasets, with the approximation being 100-1000 times faster.
Article
Genetics & Heredity
Zeyu Zhang, Yaning Yang, Yinsheng Zhou, Hongyan Fang, Min Yuan, Kate Sasser, Hisham Hamadeh, Xu Steven Xu
Summary: Mutual exclusivity analyses are effective in identifying driver genes for cancer studies, but controlling false positives and improving accuracy is challenging. A forward selection algorithm (FSME) proposed in this study for identifying mutually exclusive gene sets shows higher precision and recall rates compared to other approaches such as CoMEt, WExT, and MEGSA. Application to TCGA real datasets confirms FSME's utility in discovering cancer driver genes.
JOURNAL OF HUMAN GENETICS
(2021)
Article
Biochemical Research Methods
Su Datt Lam, M. Madan Babu, Jonathan Lees, Christine A. Orengo
Summary: Alternative splicing, specifically mutually exclusive exons (MXEs), can enhance the diversity of proteomes by altering protein specificity and selectivity while maintaining the overall protein fold. This study demonstrates that MXE-specific residues are enriched in surface exposed regions and cluster at or near protein functional sites, suggesting a role in tuning protein function. The findings suggest that small changes at critical positions on a protein surface resulting from MXE events may be important for evolutionary adaptation.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Ami G. Sangster, Robert J. Gooding, Andrew Garven, Hamid Ghaedi, David M. Berman, Scott K. Davey
Summary: Muscle invasive bladder cancer is characterized by abundant mutations, particularly in DNA damage response and chromatin modification genes. The significance of these mutations and their interactions in the development and progression of the disease have been explored through the identification of mutually exclusive mutation patterns. The discovery of these patterns sheds light on the mechanisms underlying muscle invasive bladder cancer and may guide therapeutic development.
Article
Biochemistry & Molecular Biology
Ruba Al Khalaf, Anna Bernasconi, Pietro Pinoli, Stefano Ceri
Summary: This article proposes a computational study to examine non-synonymous mutations in the genomes of SARS-CoV-2 from the beginning of the pandemic until February 2022. The researchers identify thousands of mutation pairs and analyze their evolution on the phylogenetic tree. The findings suggest that this study can explain the future mutational evolution of SARS-CoV-2.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Alfy Benny, Remya Ramakrishnan, Mahesh Hariharan
Summary: The study reveals that the Greek cross (+) stacked orientation exhibits mutually exclusive hole and electron transfer couplings in any molecular candidate, independent of the nature of the monomer. Additionally, the Greek cross (+) stacks of the considered acene candidates exhibit selective charge carrier mobility in the hopping regime of charge transport.
Review
Cell Biology
Francesca Florini, Joseph E. Visone, Kirk W. Deitsch
Summary: Cellular decision-making at the level of gene expression is crucial for the development and evolution of organisms, leading to phenotypic diversity and adaptive subpopulations. Organisms and parasites have evolved different strategies to choose one gene from a large family for expression.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Young-Soo Kwon, Sang Woo Jin, Hoseok Song
Summary: Recurring mutations in genes encoding 3' splice-site recognition proteins, U2AF1 and ZRSR2, are associated with human cancers. This study determined the binding sites of these proteins and revealed that U2AF1 recognizes U2-type splice sites, while ZRSR2 recognizes U12-type splice sites. Some sites are spliced by both U2-type and U12-type spliceosomes, suggesting that certain well-conserved motifs in U12-type introns can be recognized by the U2-type spliceosome. The nucleotides flanking U12-type intron splice sites are different from those flanking U2-type introns.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Computer Science, Information Systems
Huimin Zhang, Yi Shi, Wu Xie
Summary: In multi-agent systems, coordinating and controlling each agent to complete tasks on mutually exclusive resources is a basic mission due to the high cost of some hardware and software in reality. However, when applying supervisory control theory (SCT) to MAS, the size of the plant model increases exponentially with the number of agents, leading to a state explosion problem. To address this issue, a synchronous product with constraints and a framework for computing the supremal supervisor for the entire MAS are proposed. Experimental studies show the effectiveness of the proposed approach. The research contributes to mitigating the state explosion problem in supervisory control of MAS and eliminates the need for an additional coordinator compared to decentralized or distributed control.
Article
Pharmacology & Pharmacy
Yongyi Bai, Haishen Yao, Xuehan Jiang, Suyan Bian, Jinghui Zhou, Xingzhi Sun, Gang Hu, Lan Sun, Guotong Xie, Kunlun He
Summary: This study proposes a method to construct a nonmutually exclusive decision tree for medication recommendations for complicated diseases such as HF, and applies it in a CDSS. Our framework is universal for most diseases and could be generally applied in developing the CDSS for treatment.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Xuan Liu, Wanru Du, Xiaoyin Wang, Ruiqun Li, Pengcheng Sun, Xiaochuan Jing
Summary: This paper proposes a mutually exclusive Binary Cross Tagging (BCT) scheme and develops an end-to-end BCT framework to jointly extract overlapping entities and triples. The proposed framework achieves encouraging performance in F1 scores on multiple datasets, especially when the overlapping problem becomes complex.
Article
Engineering, Marine
H. C. Seyffert
Summary: This study develops a non-linear Design Loads Generator process to examine extreme responses of marine systems by linking wave profiles with a probabilistic framework. Analysis of rare wave groups results in an ensemble of short wave profiles to excite converged extreme value statistics of defined responses.
Review
Pediatrics
Enza D'Auria, Martina Minutoli, Alessandra Colombo, Marco Ugo Andrea Sartorio, Fiammetta Zunica, Gianvincenzo Zuccotti, Vassilios Lougaris
Summary: In recent decades, there has been a simultaneous increase in the prevalence of atopic and autoimmune disorders in pediatric population. While the Th1-Th2 paradigm suggests separate immune responses for autoimmune diseases and hypersensitivity reactions, recent evidence indicates that these diseases may share common pathogenic pathways.
FRONTIERS IN PEDIATRICS
(2023)
Article
Medicine, Research & Experimental
Alexandre de Nonneville, Sebastien Salas, Francois Bertucci, Alexander P. Sobinoff, Jose Adelaide, Arnaud Guille, Pascal Finetti, Jane R. Noble, Dimitri Churikov, Max Chaffanet, Elise Lavit, Hilda A. Pickett, Corinne Bouvier, Daniel Birnbaum, Roger R. Reddel, Vincent Geli
Summary: This study finds that in most high-grade pediatric osteosarcomas, telomere length is maintained by the alternative lengthening of telomeres (ALT) mechanism, instead of being repressed by the ATRX complex. The study identifies TOP3A as a major player in ALT and suggests it as a potential therapeutic target.
EMBO MOLECULAR MEDICINE
(2022)
Article
Computer Science, Information Systems
Taegeun Moon, Hyoungshick Kim, Sangwon Hyun
Summary: To counter compression side-channel attacks (CSCA), researchers propose Mutexion, a highly efficient CSCA mitigation system that allows full compression of web pages, including secret data, by excluding certain subsequences. They develop automated annotation techniques to trace secret and user-controlled data in web pages. Evaluation results demonstrate that Mutexion effectively prevents CSCA while achieving a similar compression ratio as vulnerable zlib.
ACM TRANSACTIONS ON THE WEB
(2022)
Article
Biotechnology & Applied Microbiology
Simone Zaccaria, Benjamin J. Raphael
Summary: Single-cell barcoding technologies enable simultaneous genome sequencing of thousands of individual cells, but with low sequencing coverage per cell. A method called CHISEL was introduced to infer allele- and haplotype-specific copy numbers in single cells and subpopulations by aggregating sparse signal across hundreds or thousands of individual cells. Application of CHISEL to single-cell sequencing datasets from breast cancer patients identified extensive allele-specific copy-number aberrations affecting genomic regions containing well-known breast cancer genes.
NATURE BIOTECHNOLOGY
(2021)
Article
Cell Biology
Jian Carrot-Zhang, Xiaotong Yao, Siddhartha Devarakonda, Aditya Deshpande, Jeffrey S. Damrauer, Tiago Chedraoui Silva, Christopher K. Wong, Hyo Young Choi, Ina Felau, A. Gordon Robertson, Mauro A. A. Castro, Lisui Bao, Esther Rheinbay, Eric Minwei Liu, Tuan Trieu, David Haan, Christina Yau, Toshinori Hinoue, Yuexin Liu, Ofer Shapira, Kiran Kumar, Karen L. Mungall, Hailei Zhang, Jake June-Koo Lee, Ashton Berger, Galen F. Gao, Binyamin Zhitomirsky, Wen-Wei Liang, Meng Zhou, Sitapriya Moorthi, Alice H. Berger, Eric A. Collisson, Michael C. Zody, Li Ding, Andrew D. Cherniack, Gad Getz, Olivier Elemento, Christopher C. Benz, Josh Stuart, J. C. Zenklusen, Rameen Beroukhim, Jason C. Chang, Joshua D. Campbell, D. Neil Hayes, Lixing Yang, Peter W. Laird, John N. Weinstein, David J. Kwiatkowski, Ming S. Tsao, William D. Travis, Ekta Khurana, Benjamin P. Berman, Katherine A. Hoadley, Nicolas Robine, Matthew Meyerson, Ramaswamy Govindan, Marcin Imielinski
Summary: Alterations in the RTK/RAS/RAF pathway are a characteristic feature of lung adenocarcinoma (LUAD). A study using whole-genome sequencing of 85 cases initially identified as RPA(-) revealed that around 33% of cases were actually RPA(+). The remaining cases showed genetic mutations associated with tumor suppressor deletions and genome instability.
Article
Biochemistry & Molecular Biology
Stefan C. Dentro, Ignaty Leshchiner, Kerstin Haase, Maxime Tarabichi, Jeff Wintersinger, Amit G. Deshwar, Kaixian Yu, Yulia Rubanova, Geoff Macintyre, Jonas Demeulemeester, Ignacio Vazquez-Garcia, Kortine Kleinheinz, Dimitri G. Livitz, Salem Malikic, Nilgun Donmez, Subhajit Sengupta, Pavana Anur, Clemency Jolly, Marek Cmero, Daniel Rosebrock, Steven E. Schumacher, Yu Fan, Matthew Fittall, Ruben M. Drews, Xiaotong Yao, Thomas B. K. Watkins, Juhee Lee, Matthias Schlesner, Hongtu Zhu, David J. Adams, Nicholas McGranahan, Charles Swanton, Gad Getz, Paul C. Boutros, Marcin Imielinski, Rameen Beroukhim, S. Cenk Sahinalp, Yuan Ji, Martin Peifer, Inigo Martincorena, Florian Markowetz, Ville Mustonen, Ke Yuan, Moritz Gerstung, Paul T. Spellman, Wenyi Wang, Quaid D. Morris, David C. Wedge, Peter Van Loo
Summary: By extensively characterizing intra-tumor heterogeneity (ITH) across 2,658 cancer samples spanning 38 cancer types, this study found evidence of distinct subclonal expansions in nearly all informative samples, with frequent branching relationships between subclones. Positive selection of subclonal driver mutations was observed across most cancer types, indicating the importance of ITH and its drivers in tumor evolution.
Article
Multidisciplinary Sciences
Kuan-lin Huang, Adam D. Scott, Daniel Cui Zhou, Liang-Bo Wang, Amila Weerasinghe, Abdulkadir Elmas, Ruiyang Liu, Yige Wu, Michael C. Wendl, Matthew A. Wyczalkowski, Jessika Baral, Sohini Sengupta, Chin-Wen Lai, Kelly Ruggles, Samuel H. Payne, Benjamin Raphael, David Fenyo, Ken Chen, Gordon Mills, Li Ding
Summary: Advances in mass-spectrometry have led to the generation of large-scale proteomics datasets containing tens of thousands of phosphorylation sites. Using a bioinformatics tool called HotPho, researchers identified 474 hybrid clusters of phosphosites and cancer mutations on protein structures, highlighting nearly 3,000 likely functional mutations and over 1,000 cancer phosphosites for potential clinical relevance.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Gryte Satas, Simone Zaccaria, Mohammed El-Kebir, Benjamin J. Raphael
Summary: DeCiFer is a new algorithm that improves the estimation of cancer cell fraction (CCF) by utilizing the descendant cell fraction (DCF), providing more accurate quantification of tumor heterogeneity and evolution.
Article
Biochemical Research Methods
Ron Zeira, Max Land, Alexander Strzalkowski, Benjamin J. Raphael
Summary: PASTE is a method for aligning and integrating spatial transcriptomics data from adjacent tissue slices, which utilizes transcriptomic similarity and spatial coordinates to increase downstream analysis power. PASTE accurately aligns spots, constructs 3D alignments or integrates into a consensus slice, and improves the identification of cell types and differentially expressed genes.
Article
Neurosciences
Sasi Arunachalam, Karol Szlachta, Samuel W. Brady, Xiaotu Ma, Bensheng Ju, Bridget Shaner, Heather L. Mulder, John Easton, Benjamin J. Raphael, Matthew Myers, Christopher Tinkle, Sariah J. Allen, Brent A. Orr, Cynthia J. Wetmore, Suzanne J. Baker, Jinghui Zhang
Summary: This study investigates the tumor invasion patterns in diffuse midline gliomas with H3 K27 alteration. The findings reveal the existence of multiple waves of invasion and the association between somatic mutations and convergent evolution. The results provide insights for the design of future clinical trials.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Editorial Material
Oncology
Shree Bose, Margarida Barroso, Milan G. Chheda, Hans Clevers, Elena Elez, Salma Kaochar, Scott E. Kopetz, Xiao-Nan Li, Funda Meric-Bernstam, Clifford A. Meyer, Haiwei Mou, Kristen M. Naegle, Martin F. Pera, Zinaida Perova, Katerina A. Politi, Benjamin J. Raphael, Paul Robson, Rosalie C. Sears, Josep Tabernero, David A. Tuveson, Alana L. Welm, Bryan E. Welm, Christopher D. Willey, Konstantin Salnikow, Jeffrey H. Chuang, Xiling Shen
Summary: 3D patient tumor avatars hold great promise for precision medicine, but their clinical benefits need to be established through standardization and prospective trials. Innovative trial designs and integrated platforms combining diagnostics and therapeutics can accelerate the development of new treatments for refractory diseases.
Article
Biochemistry & Molecular Biology
Cong Ma, Uthsav Chitra, Shirley Zhang, Benjamin J. Raphael
Summary: Spatially resolved transcriptomics technology allows for the measurement of gene expression at known locations in tissue slices, enabling the identification of spatially varying genes or cell types. This study proposes a model and algorithm for SRT data from layered tissues that considers both continuous and discrete spatial variation in gene expression. The algorithm accurately identifies tissue layers and biologically meaningful spatially varying genes in SRT data from the brain and skin.
Article
Multidisciplinary Sciences
Di Zhang, Yanxiang Deng, Petra Kukanja, Eneritz Agirre, Marek Bartosovic, Mingze Dong, Cong Ma, Sai Ma, Graham Su, Shuozhen Bao, Yang Liu, Yang Xiao, Gorazd B. Rosoklija, Andrew J. Dwork, J. John Mann, Kam W. Leong, Maura Boldrini, Liya Wang, Maximilian Haeussler, Benjamin J. Raphael, Yuval Kluger, Goncalo Castelo-Branco, Rong Fan
Summary: Emerging spatial technologies such as spatial transcriptomics and spatial epigenomics have become powerful tools in profiling cellular states in tissue contexts. However, current methods only capture one layer of omics information at a time, limiting the examination of mechanistic relationships in molecular biology. In this study, two technologies are presented for joint profiling of the epigenome and transcriptome at a genome-wide, spatially resolved, and near-single-cell resolution. These technologies provide new insights into spatial epigenetic priming, differentiation, and gene regulation within tissue architecture.
Article
Oncology
Sanjana Rajan, Simone Zaccaria, Matthew V. Cannon, Maren Cam, Amy C. Gross, Benjamin J. Raphael, Ryan D. Roberts
Summary: Osteosarcoma is a malignancy with high genomic complexity. Through single-cell DNA sequencing, it is found that despite extensive structural complexity, there is a high degree of cell-cell homogeneity in these tumors with little subclonal diversification. Longitudinal analysis also shows that most somatic copy-number aberrations (SCNAs) are acquired early in the oncogenic process and are preserved over tumor evolution. These findings have implications for diagnosis, biomarker assessment, and understanding tumor heterogeneity and evolution.
CANCER RESEARCH COMMUNICATIONS
(2023)
Article
Biotechnology & Applied Microbiology
Palash Sashittal, Haochen Zhang, Christine A. Iacobuzio-Donahue, Benjamin J. Raphael
Summary: This article introduces a new evolutionary model and algorithm, ConDoR, for inferring phylogeny in tumors. The model uses SNVs as phylogenetic markers and constrains losses of SNVs according to clusters of cells. The advantages of ConDoR are demonstrated through simulations and real data.
Article
Biochemical Research Methods
Henri Schmidt, Palash Sashittal, Benjamin J. Raphael
Summary: New low-coverage single-cell DNA sequencing technologies enable the inference of tumor evolutionary history by modeling copy number aberrations. A widely used model is the copy number transformation (CNT) model, but no efficient algorithm has been developed to find the most parsimonious phylogeny. This study introduces the zero-agnostic copy number transformation (ZCNT) model and develops efficient algorithms for inferring phylogenies on copy number profiles.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Article
Biochemical Research Methods
Uthsav Chitra, Tae Yoon Park, Benjamin J. Raphael
Summary: A standard paradigm in computational biology is to analyze high-throughput biological data using interaction networks as prior knowledge. This study introduces NetMix2, an algorithm that combines the advantages of subnetwork families and network propagation methods to identify altered subnetworks. NetMix2 outperforms other methods in various applications.
JOURNAL OF COMPUTATIONAL BIOLOGY
(2022)
Article
Biochemical Research Methods
Matthew A. Reyna, Uthsav Chitra, Rebecca Elyanow, Benjamin J. Raphael
Summary: The identification of altered subnetworks in computational biology is a classic problem, with existing methods often producing large subnetworks that are difficult to interpret biologically. This study introduces an algorithm called NetMix, which uses Gaussian mixture models to obtain less biased estimates of altered subnetwork parameters, outperforming existing methods in identifying altered subnetworks in both simulated and real data.
JOURNAL OF COMPUTATIONAL BIOLOGY
(2021)