Review
Endocrinology & Metabolism
Aaron J. Deutsch, Emma Ahlqvist, Miriam S. Udler
Summary: The historical classification of diabetes into types 1 and 2 is limited in capturing the heterogeneity of the disease. Data-driven approaches using clinical phenotypes and/or genetic information can help refine diabetes subtypes, but implementation barriers need to be overcome.
Article
Genetics & Heredity
Amelie S. Lotz-Havla, Mathias Woidy, Philipp Guder, Jessica Schmiesing, Ralf Erdmann, Hans R. Waterham, Ania C. Muntau, Soren W. Gersting
Summary: Peroxisomes play crucial roles in cellular metabolism, with PEX26 protein being involved in various processes including matrix protein import, division, proliferation, and membrane assembly. Mutations in PEX26 can lead to a spectrum of peroxisomal disorders, impacting protein-protein interactions and cellular lipid metabolism, ultimately influencing the phenotype of patients. This study explores the complex network of PEX26 interactions within peroxisomes, shedding light on its function and potential implications for disease mechanisms.
FRONTIERS IN GENETICS
(2021)
Review
Genetics & Heredity
Purnima Kovuri, Anupama Yadav, Himanshu Sinha
Summary: Organisms can display different phenotypes in different environments, which is known as phenotypic plasticity. This plasticity helps organisms survive in new environments. By studying yeast, researchers have started to unravel the genetic architecture of phenotypic plasticity. Genetic variants and their interactions impact the phenotype in various environments, and different environments can modulate the effects of genetic variants and interactions on the phenotype. Understanding the genetic mechanisms of phenotypic plasticity can provide insights into short and long-term responses to selection and the wide variation in disease manifestation in human populations.
TRENDS IN GENETICS
(2023)
Review
Genetics & Heredity
Juan A. G. Ranea, James Perkins, Monica Chagoyen, Elena Diaz-Santiago, Florencio Pazos
Summary: Network and systemic approaches are valuable in studying human pathologies to understand molecular mechanisms and potential treatment options. The conventional partitioning of diseases into discrete categories may not adequately capture the heterogeneity of diseases. Clinical phenotypes, which are directly observable and closer to the molecular basis of pathology, play an important role in personalized medicine and are being incorporated into pathology research.
Article
Biology
James A. Watson, Carolyne M. Ndila, Sophie Uyoga, Alexander Macharia, Gideon Nyutu, Shebe Mohammed, Caroline Ngetsa, Neema Mturi, Norbert Peshu, Benjamin Tsofa, Kirk Rockett, Stije Leopold, Hugh Kingston, Elizabeth C. George, Kathryn Maitland, Nicholas P. J. Day, Arjen M. Dondorp, Philip Bejon, Thomas Williams, Chris C. Holmes, Nicholas J. White
Summary: Severe falciparum malaria has significant impact on human evolution, but genetic susceptibility studies are limited by phenotypic imprecision. Diagnostic uncertainty in young children in high malaria transmission areas prompted the development of a probabilistic diagnostic model, improving accuracy. The proposed data-tilting approach in case-control studies with phenotype mis-labeling can reduce false discovery rates and enhance statistical power in genetic association studies.
Article
Neurosciences
Ross D. Markello, Golia Shafiei, Christina Tremblay, Ronald B. Postuma, Alain Dagher, Bratislav Misic
Summary: Individuals with Parkinson's disease exhibit a complex clinical phenotype, where data fusion can capture inter-dependencies among different modalities, with neuroimaging data playing a critical role.
NPJ PARKINSONS DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Athanasios Kyritsis, Eirini Papanastasi, Ioanna Kokkori, Panagiotis Maragozidis, Demetra S. M. Chatzileontiadou, Paschalina Pallaki, Maria Labrou, Sotirios G. Zarogiannis, George P. Chrousos, Dimitrios Vlachakis, Konstantinos Gourgoulianis, Nikolaos A. A. Balatsos
Summary: The poly(A) tail at the 3' end of mRNAs plays a crucial role in their stability, translational efficiency, and degradation. Deadenylases are a family of enzymes that catalyze the shortening and removal of the poly(A) tail, thus regulating gene expression. Dysregulation of gene expression is closely associated with cancer, making the study of deadenylases essential. In this study, we found that CNOT6 and CNOT7 are the most prevalent and interconnected deadenylases. Silencing specific deadenylases affects the regulation of specific transcripts, while multiple deadenylases can have overlapping functions in regulating the same transcripts.
Article
Multidisciplinary Sciences
Daniel K. Carlin, Simon Larsen, Vikram Sirupurapu, Michael Cho, Edwin Silverman, Jan Baumbach, Trey Ideker
Summary: Many disease-causing genetic variants converge on common biological functions and pathways, but how to incorporate pathway knowledge in genetic association studies is still unclear. Previous approaches employ a two-step method, while a concise one-step approach called Hierarchical Genetic Analysis (Higana) directly computes phenotype associations against each function in the large hierarchy of biological functions documented by the Gene Ontology. Using Higana, risk genes and functions for Chronic Obstructive Pulmonary Disease (COPD) were identified, including microtubule transport, muscle adaptation, and nicotine receptor signaling pathways, which provide new insights into COPD.
Article
Medicine, General & Internal
Francois Alexandre, Virginie Molinier, Maurice Hayot, Guillaume Chevance, Gregory Moullec, Alain Varray, Nelly Heraud
Summary: This study aims to evaluate the impact of LTOT prescription outside the guidelines on the survival of COPD patients through a systematic review and individual patient data meta-analysis.
Article
Multidisciplinary Sciences
Oliver M. Crook, Kelsey Lane Warmbrod, Greg Lipstein, Christine Chung, Christopher W. Bakerlee, T. Greg McKelvey, Shelly R. Holland, Jacob L. Swett, Kevin M. Esvelt, Ethan C. Alley, William J. Bradshaw
Summary: The study aims to improve genetic engineering attribution techniques and advance the field through a public competition. The results demonstrate that new models outperformed previous ones in identifying the true lab-of-origin of engineered plasmid sequences, and new evaluation metrics showed significant improvements. The research teams employed different approaches, with one method showing advantages in speed and accuracy.
NATURE COMMUNICATIONS
(2022)
Article
Biotechnology & Applied Microbiology
Ying Zhang, Jinglu Wang, Jianjun Du, Yanxin Zhao, Xianju Lu, Weiliang Wen, Shenghao Gu, Jiangchuan Fan, Chuanyu Wang, Sheng Wu, Yongjian Wang, Shengjin Liao, Chunjiang Zhao, Xinyu Guo
Summary: This study developed an automated and high-throughput technique for rapid acquisition of maize stem vascular bundle traits. By establishing a database and conducting genome-wide association studies, multiple genes associated with vascular bundle traits were identified.
PLANT BIOTECHNOLOGY JOURNAL
(2021)
Article
Microbiology
Vineetha M. Zacharia, Yein Ra, Catherine Sue, Elizabeth Alcala, Jewel N. Reaso, Steven E. Ruzin, Matthew F. Traxler
Summary: The spatial divisions of labor in colonies of Streptomyces coelicolor are determined by a combination of physiological gradients and regulatory network architecture. Using fluorescent reporters, it was demonstrated that the pathways for antibiotic biosynthesis and aerial hypha formation are activated in distinct waves of gene expression in S. coelicolor colonies.
Article
Plant Sciences
Jun Hu, Meng Mei, Fang Jin, Jianfei Xu, Shaoguang Duan, Chunsong Bian, Guangcun Li, Xiyao Wang, Liping Jin
Summary: Phenotypic evaluation and molecular biotechnology were used to investigate the variation and diversity of 149 main potato cultivars in China. The results showed high genetic variation based on SSR markers. Population structure analysis divided the varieties into three subgroups. The STI032 marker was found to be significantly associated with tuber starch content and growth period traits.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Giulia Fiscon, Silvia Pegoraro, Federica Conte, Guidalberto Manfioletti, Paola Paci
Summary: The study utilized the SWIM software to analyze gene expression data of TNBC patients in the TCGA database, revealing a potential cooperation among the transcription factors HMGA1, FOXM1, and MYBL2 and demonstrating through in vitro experiments how they may modulate the expression of each other.
Article
Multidisciplinary Sciences
Rebecca A. Harrison, Vikram Rao, Shelli R. Kesler
Summary: Genetic polymorphisms in select genes have been associated with vulnerability to cognitive impairment, particularly in patients with breast cancer. Chemotherapy-treated breast cancer patients, especially those who are APOE e4 carriers, may experience slower processing speed. Risk-related alleles may influence functional connectivity in specific brain regions, but their impact on cognitive test performance varies.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Matthew Schwede, Levi Waldron, Samuel C. Mok, Wei Wei, Azfar Basunia, Melissa A. Merritt, Constantine S. Mitsiades, Giovanni Parmigiani, David P. Harrington, John Quackenbush, Michael J. Birrer, Aedin C. Culhane
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2020)
Article
Cell Biology
Camila M. Lopes-Ramos, Cho-Yi Chen, Marieke L. Kuijjer, Joseph N. Paulson, Abhijeet R. Sonawane, Maud Fagny, John Platig, Kimberly Glass, John Quackenbush, Dawn L. DeMeo
Article
Respiratory System
Jen-hwa Chu, Wenlan Zang, Milica Vukmirovic, Xiting Yan, Taylor Adams, Giuseppe DeIuliis, Buqu Hu, Antun Mihaljinec, Jonas C. Schupp, Michael J. Becich, Harry Hochheiser, Kevin F. Gibson, Edward S. Chen, Alison Morris, Joseph K. Leader, Stephen R. Wisniewski, Yingze Zhang, Frank C. Sciurba, Ronald G. Collman, Robert Sandhaus, Erica L. Herzog, Karen C. Patterson, Maor Sauler, Charlie Strange, Naftali Kaminski
Summary: This study investigated gene expression profiles of BAL and PBMC in AATD individuals and identified a gene module, ME31, that correlated with clinical variables and clustered AATD individuals based on disease severity. The findings suggest the presence of previously unrecognized disease endotypes in AATD associated with T-lymphocyte immunity.
Article
Multidisciplinary Sciences
Elodie Hatchi, Liana Goehring, Serena Landini, Konstantina Skourti-Stathaki, Derrick K. DeConti, Fieda O. Abderazzaq, Priyankana Banerjee, Timothy M. Demers, Yaoyu E. Wang, John Quackenbush, David M. Livingston
Summary: Strong connections are found between R-loops, genome instability, and human disease. R-loops play a role in maintaining homeostasis by regulating certain physiological processes, such as the synthesis of antisense transcripts through transcription termination pause sites. A species of single-stranded, DNA-damage-associated small RNA (sdRNA) generated by a BRCA1-RNAi complex promotes DNA repair at transcriptional termination pause sites forming R-loops.
Article
Mathematical & Computational Biology
Albert T. Young, Xavier Carette, Michaela Helmel, Hanno Steen, Robert N. Husson, John Quackenbush, John Platig
Summary: The inhibition of Mtb serine/threonine protein kinases PknA and PknB leads to changes in the TF regulatory network, affecting regulatory programs involved in cell wall integrity, stress response, and energy production. This highlights the importance of incorporating signal-driven TF modifications in regulatory network approaches.
NPJ SYSTEMS BIOLOGY AND APPLICATIONS
(2021)
Article
Oncology
Camila M. Lopes-Ramos, Tatiana Belova, Tess H. Brunner, Marouen Ben Guebila, Daniel Osorio, John Quackenbush, Marieke L. Kuijjer
Summary: Analysis identified seven pathways associated with survival in glioblastoma patients, with dysregulation of PD1 signaling correlating with poor prognosis. This suggests a new approach to predict patient survival and highlights potential therapeutic interventions based on gene regulatory network analysis.
Article
Biochemistry & Molecular Biology
Marouen Ben Guebila, Camila M. Lopes-Ramos, Deborah Weighill, Abhijeet Rajendra Sonawane, Rebekka Burkholz, Behrouz Shamsaei, John Platig, Kimberly Glass, Marieke L. Kuijjer, John Quackenbush
Summary: Gene regulation networks play a crucial role in tissue identity, disease development, and therapeutic response. The GRAND database provides computationally-inferred gene regulatory network models and targeting scores for predicting drug effects on network structures and matching potential therapeutic drugs to disease states.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Cell Biology
Rebekka Burkholz, John Quackenbush, Daniel Bojar
Summary: Glycans pose substantial challenges for computational biology due to their nonlinear and diverse nature. Sweet-Net, a graph convolutional neural network, outperforms other computational methods in predicting glycan properties and can learn representations that are predictive of organismal phenotypic and environmental properties. Additionally, glycan-focused machine learning can be used to predict viral glycan binding and discover viral receptors.
Article
Biochemistry & Molecular Biology
Deborah Weighill, Marouen Ben Guebila, Kimberly Glass, John Quackenbush, John Platig
Summary: Understanding how individual genotypes influence gene regulation can improve our understanding of human health and development. EGRET is a method that infers genotype-specific gene regulatory networks to reveal the genetic associations driving complex phenotypes.
Article
Mathematical & Computational Biology
Abhijeet Rajendra Sonawane, Dawn L. DeMeo, John Quackenbush, Kimberly Glass
Summary: The study focuses on the application of epigenetic data in gene regulatory networks, developing the SPIDER method for network reconstruction, which shows high accuracy and cell-line-specific interactions, and has the potential to identify novel hypotheses for better characterizing cell-type and phenotype-specific regulatory mechanisms.
NPJ SYSTEMS BIOLOGY AND APPLICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Katherine H. Shutta, Deborah Weighill, Rebekka Burkholz, Marouen Ben Guebila, Dawn L. DeMeo, Helena U. Zacharias, John Quackenbush, Michael Altenbuchinger
Summary: In this study, we propose a network approach based on Gaussian Graphical Models (GGMs) called DRAGON, which allows for the joint analysis of multi-omic data. DRAGON adapts to the differences between omics layers, improving model inference and edge recovery, and can identify key molecular mechanisms.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemical Research Methods
Sheila M. Gaynor, Maud Fagny, Xihong Lin, John Platig, John Quackenbush
Summary: This study constructed twenty-nine tissue-specific eQTL networks using GTEx data and evaluated different network specifications. The researchers found that using a thresholded Benjamini-Hochberg q value weighted by the Z-statistic balanced metric reproducibility and computational efficiency. The eQTL networks were complementary to gene regulatory networks in understanding regulation, and highly connected nodes were enriched for tissue-relevant traits.
CELL REPORTS METHODS
(2022)
Article
Genetics & Heredity
Marouen Ben Guebila, Daniel C. Morgan, Kimberly Glass, Marieke L. Kuijjer, Dawn L. DeMeo, John Quackenbush
Summary: Gene regulatory network inference allows for modeling genome-scale regulatory processes. Researchers have developed a collection of tools to model various regulatory processes and improve their performance through GPU-accelerated calculations.
NAR GENOMICS AND BIOINFORMATICS
(2022)
Article
Urology & Nephrology
Kinsuk Chauhan, Girish N. Nadkarni, Fergus Fleming, James McCullough, Cijiang J. He, John Quackenbush, Barbara Murphy, Michael J. Donovan, Steven G. Coca, Joseph Bonventre
Article
Computer Science, Information Systems
Jipeng Qiang, Wei Ding, Marieke Kuijjer, John Quackenbush, Ping Chen
