Article
Multidisciplinary Sciences
Md Tauhidul Islam, Lei Xing
Summary: The authors develop a cartography strategy based on gene-gene interactions to transform high-dimensional gene expression data into a spatially configured genomap, enabling accurate deep pattern discovery. This approach presents significant challenges and opportunities in the field of single cell genomics for biomedical research. The unique cartography method captures gene interactions in the spatial configuration of genomaps, allowing for the extraction of deep genomic interaction features and the discovery of discriminative patterns in the data.
NATURE COMMUNICATIONS
(2023)
Article
Genetics & Heredity
Yulin Dai, Hui Yu, Qiheng Yan, Bingrui Li, Andi Liu, Wendao Liu, Xiaoqian Jiang, Yejin Kim, Yan Guo, Zhongming Zhao
Summary: This study conducted literature mining and protein-protein interaction analysis to identify a core gene network associated with COVID-19. The network was found to be enriched with genes related to immune cell function, cellular signaling cascade, and severe symptoms of COVID-19. These findings have implications for drug discovery and repurposing to combat SARS-CoV-2 and other severe infectious diseases.
Review
Biochemistry & Molecular Biology
Parasvi S. Patel, Arash Algouneh, Razq Hakem
Summary: The principle of synthetic lethality, aiming at disrupting two genes to eliminate tumors, particularly in BRCA1/2-mutated cancers, has been a focus in cancer research. Although PARP inhibitors have shown clinical success in certain cases, resistance remains an issue and the exploration of alternative targets is crucial for future therapies. Various synthetic lethal interactors of BRCA1/2 have been identified, providing potential avenues for the development of new targeted therapies.
Article
Biochemical Research Methods
Xinguo Lu, Guanyuan Chen, Jinxin Li, Xiangjin Hu, Fengxu Sun
Summary: Synthetic lethality is a potential cancer therapeutic strategy and drug discovery method. Using computational approaches to predict synthetic lethality genes can effectively complement time-consuming and costly wet experiments. In this study, a Multiple Attention Graph Convolution Networks (MAGCN) approach is proposed, which aggregates neighborhood information from multiple heterogeneous graphs to predict synthetic lethality.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2023)
Article
Geochemistry & Geophysics
Jun-Hyung Kim, Youngbae Hwang
Summary: This study proposes a method for generating synthetic training data for infrared small target detection, addressing the scarcity of training data. The generative adversarial network framework is adopted to generate synthetic background images and infrared small targets through independent processes. Experimental results demonstrate that training detection networks using a dataset composed of both real and synthetic images leads to better performance compared to using real data only.
IEEE TRANSACTIONS ON GEOSCIENCE AND REMOTE SENSING
(2022)
Article
Biochemical Research Methods
Minwoo Pak, Sangseon Lee, Inyoung Sung, Bonil Koo, Sun Kim
Summary: Drug response prediction (DRP) is crucial for precision medicine to anticipate patient reactions to drugs. While most studies use cell line transcriptome data and drug chemical structures to predict drug response, this study proposes a framework that leverages drug target interaction (DTI) information to improve deep learning-based DRP models. By computing gene perturbation scores through network propagation techniques, the framework integrates this DTI information with existing DRP models. The results show significant performance boosts, especially when dealing with unknown drugs.
BRIEFINGS IN BIOINFORMATICS
(2023)
Review
Immunology
Matthew B. B. McNeil, Chen-Yi Cheung, Natalie J. E. Waller, Cara Adolph, Cassandra L. L. Chapman, Noon E. J. Seeto, William Jowsey, Zhengqiu Li, H. M. Adnan Hameed, Tianyu Zhang, Gregory M. M. Cook
Summary: This review discusses the consequences of inhibiting multiple respiratory components of Mycobacterium tuberculosis and provides potential mechanisms for the strongest interactions. By highlighting interactions with alternative respiratory components, alternative proteins can be explored as potential drug targets and as part of unique drug combinations.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Shenghui Weng, Hang Ruan
Summary: Synthetic lethality (SL) refers to the occurrence of non-lethal disordered genes that can lead to cell death when they co-occur. SL-based anticancer therapeutics can selectively kill cancer cells with targeted mutated genes while sparing normal cells. By combining comprehensive multi-omics data analysis and experimental validation of one SL gene pair, Guo et al. have provided a systematic overview of cancer-specific SL interactions, which could enhance our understanding of carcinogenesis and potentially aid in the identification of anticancer therapeutic targets.
Review
Pharmacology & Pharmacy
Zekun Zeng, Wenfang Zheng, Peng Hou
Summary: Drug-metabolizing enzymes (DMEs) play an important role in anticancer therapy, not only influencing the action of anticancer drugs, but also being closely associated with pathological and biochemical changes during tumor progression. Synthetic lethal strategy, using unique genetic markers to discover selectively targeted anticancer drugs for cancer cells, has become more accessible. Dysregulation of DMEs has been found in various cancers, making them potential candidates for synthetic lethal strategy.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Multidisciplinary Sciences
Javier Santos-Moreno, Eve Tasiudi, Hadiastri Kusumawardhani, Joerg Stelling, Yolanda Schaerli
Summary: Genotype networks are sets of genotypes connected by small mutational changes that share the same phenotype. The authors combine construction of over 20 synthetic gene regulatory networks with mathematical modeling to exemplify how gene regulatory networks provide robustness in face of mutations while enabling transitions to innovative phenotypes.
NATURE COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Yahui Long, Min Wu, Yong Liu, Jie Zheng, Chee Keong Kwoh, Jiawei Luo, Xiaoli Li
Summary: The researchers proposed a novel graph contextualized attention network (GCATSL) for learning gene representations for synthetic lethality (SL) prediction. Their method demonstrated superior performance in experiments, outperforming 14 existing methods in predicting SL interactions more effectively, and identifying novel SL pairs.
Review
Oncology
Ananna Bhadra Arna, Hardikkumar Patel, Ravi Shankar Singh, Frederick S. Vizeacoumar, Anthony Kusalik, Andrew Freywald, Franco J. Vizeacoumar, Yuliang Wu
Summary: DEAD/H-box helicases play important roles in various aspects of RNA metabolism and their dysregulation is associated with cancer. Synthetic lethality (SL) and synthetic dosage lethality (SDL) approaches, which exploit genetic interactions among cancer-related genes, have shown promise in cancer research. This review analyzes the gene expression of DEAD/H-box helicases in different cancer types and discusses the potential therapeutic applications of their SL/SDL interactions. The latest developments in clinical applications and challenges in targeting DEAD/H-box helicases for drug discovery are also discussed.
FRONTIERS IN ONCOLOGY
(2023)
Review
Oncology
Beatrice Balboni, Francesco Rinaldi, Viola Previtali, Andrea Ciamarone, Stefania Girotto, Andrea Cavalli
Summary: RAD52 is a non-essential DNA/RNA-binding protein involved in DNA repair mechanisms. Its inhibition has been shown to be synthetically lethal in cancer cells and is considered a potential target. However, detailed understanding of RAD52's structure and mechanisms is still limited, and no preclinical inhibitors have been identified.
Review
Oncology
Kun Yao, Hua Liu, Jiajun Yin, Jianmin Yuan, Hong Tao
Summary: The article discusses mutated isocitrate dehydrogenase 1/2 (mIDH1/2) and related treatment strategies, such as synthetic lethal interactions and synergistic therapies. Opportunities and challenges for translating these strategies into clinic to combat the defects of mIDH1/2 inhibitors are explored.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Biochemical Research Methods
Yan Zhu, Yuhuan Zhou, Yang Liu, Xuan Wang, Junyi Li
Summary: Synthetic lethality is a genetic interaction that selectively kills cancer cells without harming normal cells. This study proposes a novel SL prediction method, SLGNN, based on a gene-related knowledge graph. The SLGNN model outperforms existing methods and provides better interpretability for predicting and explaining SL interactions.
Article
Biochemistry & Molecular Biology
Cecil J. Howard, Brendan M. Floyd, Angela M. Bardo, Jagannath Swaminathan, Edward M. Marcotte, Eric Anslyn
ACS CHEMICAL BIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Claire D. McWhite, Ophelia Papoulas, Kevin Drew, Rachael M. Cox, Viviana June, Oliver Xiaoou Dong, Taejoon Kwon, Cuihong Wan, Mari L. Salmi, Stanley J. Roux, Karen S. Browning, Z. Jeffrey Chen, Pamela C. Ronald, Edward M. Marcotte
Article
Cell Biology
Heidi M. Blank, Ophelia Papoulas, Nairita Maitra, Riddhiman Garge, Brian K. Kennedy, Birgit Schilling, Edward M. Marcotte, Michael Polymenis
MOLECULAR BIOLOGY OF THE CELL
(2020)
Article
Genetics & Heredity
Riddhiman K. Garge, Jon M. Laurent, Aashiq H. Kachroo, Edward M. Marcotte
Article
Chemistry, Organic
Alexander A. Boulgakov, Sarah R. Moor, Hyun Hwa Jo, Pedro Metola, Leo A. Joyce, Edward M. Marcotte, Christopher J. Welch, Eric Anslyn
JOURNAL OF ORGANIC CHEMISTRY
(2020)
Article
Biochemical Research Methods
Brendan M. Floyd, Kevin Drew, Edward M. Marcotte
Summary: Protein phosphorylation is a crucial regulatory mechanism in eukaryotic cellular processes, with the majority of phosphorylation sites still having unknown functions. A method called phospho-DIFFRAC was developed to systematically identify phosphorylation-dependent protein assemblies and found that these interactions are enriched in RNA-binding proteins.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Kevin Drew, John B. Wallingford, Edward M. Marcotte
Summary: Researchers developed a machine learning framework to identify nearly 7,000 protein complexes in human cells, resulting in the creation of the more accurate and comprehensive resource hu.MAP 2.0 and proposing many new hypotheses. The study also identified promiscuous proteins that participate in multiple complexes, suggesting potential moonlighting roles.
MOLECULAR SYSTEMS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Caitlyn L. McCafferty, David W. Taylor, Edward M. Marcotte
Summary: Electron microscopy (EM) provides near-atomic resolution structures for proteins, but some structures are limited. Researchers have developed a new method that incorporates co-evolutionary information to build three-dimensional models of atomic structures for fitting into EM maps. This method improves systematic fitting of atomic models into medium- to low-resolution EM maps, enhancing integrative models lacking spatial data.
Article
Developmental Biology
Elle C. Roberson, Anna M. Battenhouse, Riddhiman K. Garge, Ngan Kim Tran, Edward M. Marcotte, John B. Wallingford
Summary: This study found significant gene expression differences along the anteroposterior axis of the mouse oviduct, but relatively few changes in gene expression across the estrous cycle. The gene expression variances along the anteroposterior axis included genes related to embryonic development. The researchers speculated that the stable transcriptional dynamics in the mouse oviduct across the estrous cycle may be influenced by its extremely rapid five-day cycle.
DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Caitlin C. Devitt, Chanjae Lee, Rachael M. Cox, Ophelia Papoulas, Jose Alvarado, Shashank Shekhar, Edward M. Marcotte, John B. Wallingford
Summary: The study focuses on the role of Twf1 in vertebrate gastrulation and finds that Twf1 is crucial for convergent extension. Loss of Twf1 disrupts lamellipodial dynamics and polarity and prevents the assembly of polarized cytoplasmic actin cables necessary for convergent extension. This research provides new insights into the specific cell behaviors of embryonic morphogenesis and their connection to the core machinery of actin regulation.
JOURNAL OF CELL SCIENCE
(2021)
Article
Biochemical Research Methods
Javier Antonio Alfaro, Peggy Bohlander, Mingjie Dai, Mike Filius, Cecil J. Howard, Xander F. van Kooten, Shilo Ohayon, Adam Pomorski, Sonja Schmid, Aleksei Aksimentiev, Eric V. Anslyn, Georges Bedran, Chan Cao, Mauro Chinappi, Etienne Coyaud, Cees Dekker, Gunnar Dittmar, Nicholas Drachman, Rienk Eelkema, David Goodlett, Sebastien Hentz, Umesh Kalathiya, Neil L. Kelleher, Ryan T. Kelly, Zvi Kelman, Sung Hyun Kim, Bernhard Kuster, David Rodriguez-Larrea, Stuart Lindsay, Giovanni Maglia, Edward M. Marcotte, John P. Marino, Christophe Masselon, Michael Mayer, Patroklos Samaras, Kumar Sarthak, Lusia Sepiashvili, Derek Stein, Meni Wanunu, Mathias Wilhelm, Peng Yin, Amit Meller, Chirlmin Joo
Summary: Single-cell profiling methods have greatly impacted the understanding of cellular heterogeneity, although proteome profiling at the single-cell level is still in the early stages. The development of new technologies, such as single-molecule protein sequencing and innovations in mass spectrometry, will eventually enable broad sequence coverage in single-cell proteomics, leading to new biological discoveries and opportunities for ultra-sensitive disease diagnostics.
Article
Obstetrics & Gynecology
Rami Vanguri, Jamal Benhamida, Jonathan H. Young, Yanyun Li, Oliver Zivanovic, Dennis Chi, Alexandra Snyder, Travis J. Hollmann, Katherine L. Mager
Summary: This study quantitatively characterized the temporal and spatial expression changes of repressive and stimulatory checkpoints in immune cell populations in high grade serous ovarian carcinomas (HGSOC) before and after neoadjuvant platinum-based chemotherapy. The results showed that the expression of inhibitory and stimulatory proteins changed post-treatment, resulting in immune compositions more favorable to checkpoint modulations, suggesting potential therapeutic strategies for recurrent HGSOC.
GYNECOLOGIC ONCOLOGY REPORTS
(2022)
Article
Gastroenterology & Hepatology
Yannis K. Valtis, Trevor Barlowe, Jonathan H. Young, Andrew H. Lichtman, Lei Zhao, Jason L. Hornick, James M. Cleary, Nikroo Hashemi, Alan Cubre, Rebecca M. Baron
Summary: This case report presents a rare instance of intrahepatic cholangiocarcinoma accompanied by acute liver failure. The patient ultimately died of refractory shock attributed to sepsis and fulminant liver failure. Autopsy revealed diffuse intrahepatic cholangiocarcinoma with metastases to regional lymph nodes and intravascular spread to the lungs.
CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY
(2022)
Article
Biochemical Research Methods
Claire D. McWhite, Ophelia Papoulas, Kevin Drew, Vy Dang, Janelle C. Leggere, Wisath Sae-Lee, Edward M. Marcotte
Summary: CF/MS is a flexible and powerful method for detecting physical associations of proteins, which can be applied to any tissue or organism without the need for protein-specific antibodies or epitope tags. Successful application of this approach relies on sample preparation protocols and a computational pipeline.
Article
Biochemistry & Molecular Biology
Caitlyn L. McCafferty, Edward M. Marcotte, David W. Taylor
Summary: Protein-protein interactions and the prediction of pairwise protein interaction interfaces were studied, utilizing a reduced representation of protein geometry and mapping of molecular properties. The research demonstrated comparable predictions to other structure-based tools and tolerance to conformational changes, highlighting the enhanced speed and capabilities of the simplified approach.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2021)