Article
Genetics & Heredity
Thomas J. Nicholas, Michael J. Cormier, Xiaomeng Huang, Yi Qiao, Gabor T. Marth, Aaron R. Quinlan
Summary: OncoGEMINI is a new tool for exploring the patterns and trajectories of mutations in tumors, enabling quick identification of potential drivers of mutation evolution.
Article
Biochemistry & Molecular Biology
Sebastian Lunke, Sophie. E. E. Bouffler, Chirag. V. V. Patel, Sarah. A. A. Sandaradura, Meredith Wilson, Jason Pinner, Matthew. F. F. Hunter, Christopher. P. P. Barnett, Mathew Wallis, Benjamin Kamien, Tiong. Y. Y. Tan, Mary-Louise Freckmann, Belinda Chong, Dean Phelan, David Francis, Karin. S. S. Kassahn, Thuong Ha, Song Gao, Peer Arts, Matilda. R. S. R. Jackson, Hamish. S. S. Scott, Stefanie Eggers, Simone Rowley, Kirsten Boggs, Ana Rakonjac, Gemma. R. R. Brett, Michelle. G. G. de Silva, Amanda Springer, Michelle Ward, Kirsty Stallard, Cas Simons, Thomas Conway, Andreas Halman, Nicole. J. J. Van Bergen, Tim Sikora, Liana. N. N. Semcesen, David. A. A. Stroud, Alison. G. G. Compton, David. R. R. Thorburn, Katrina. M. M. Bell, Simon Sadedin, Kathryn. N. N. North, John Christodoulou, Zornitza Stark
Summary: A report from the Australian Acute Care Genomics programme demonstrates the clinical utility of integrating rapid whole-genome sequencing and multi-omic analyses in diagnosing and treating critically ill infants and children with rare diseases. Over a span of 2 years, the program provided whole-genome sequencing to 290 families and achieved a diagnostic yield of 54%. The results highlight the potential of incorporating multi-omic approaches into mainstream diagnostic practice for rare disease genomic testing.
Article
Biochemistry & Molecular Biology
Miaomiao Chen, Weizhi Zhang, Yujie Gou, Danyang Xu, Yuxiang Wei, Dan Liu, Cheng Han, Xinhe Huang, Chengzhi Li, Wanshan Ning, Di Peng, Yu Xue
Summary: In this study, an updated server called Group-based Prediction System (GPS) 6.0 was reported for predicting PK-specific phosphorylation sites in eukaryotes. By training and transfer learning, GPS 6.0 could hierarchically predict PK-specific p-sites for 44046 PKs in 185 species and provide additional knowledge for annotation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Naomichi Takemata, Stephen D. Bell
Summary: Chromosome conformation capture technologies have identified topologically associating domains and A/B compartments as key features of eukaryotic chromosomes, with Sulfolobus archaea chromosomes also showing unique characteristics. The study reveals local rules governing the organization of topological domains and provides insights into the evolution of eukaryotic chromosome conformation through analysis of prokaryotic chromosome structures.
Review
Biotechnology & Applied Microbiology
Ian C. Tobias, Luis E. Abatti, Sakthi D. Moorthy, Shanelle Mullany, Tiegh Taylor, Nawrah Khader, Mario A. Filice, Jennifer A. Mitchell
Summary: Enhancers are cis-regulatory sequences distal to target genes that coordinate gene expression in a tissue-specific manner. Identifying enhancers is challenging, but recent developments in prediction methods have improved our ability to manipulate and observe enhancers in vitro.
Article
Chemistry, Medicinal
Maximilian Beckers, Noe Sturm, Finton Sirockin, Nikolas Fechner, Nikolaus Stiefl
Summary: Early assessment of compound potential is a major challenge in computer-assisted drug design. This study presents a novel deep learning approach that utilizes large-scale predictions to evaluate the potential of compounds as drug candidates, achieving better results than previous methods.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Michael P. Wilczek, Aiden M. C. Pike, Sophie E. Craig, Melissa S. Maginnis, Benjamin L. King
Summary: This study examines the mutations in the noncoding control region (NCCR) of JC polyomavirus (JCPyV) and their influence on viral transcription. It was found that the number of transcription factor binding sites (TFBS) significantly increased in patients with progressive multifocal leukoencephalopathy (PML), especially in samples isolated from the cerebrospinal fluid. These findings suggest that the rearrangements in NCCR can impact disease outcome by altering viral gene transcription.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell & Tissue Engineering
Gal Keshet, Nissim Benvenisty
Summary: This study demonstrates that naive hPSCs exhibit high levels of non-random loss of imprinting, with a bias towards paternally methylated imprinting control regions. The extent of loss of imprinting is tightly correlated with FGF signaling, showing the importance of these events in disease modeling, development, and cell therapy.
Article
Multidisciplinary Sciences
Elodie Bal, Rahul Kumar, Mohammad Hadigol, Antony B. Holmes, Laura K. Hilton, Jui Wan Loh, Kostiantyn Dreval, Jasper C. H. Wong, Sofija Vlasevska, Clarissa Corinaldesi, Rajesh Kumar Soni, Katia Basso, Ryan D. Morin, Hossein Khiabanian, Laura Pasqualucci, Riccardo Dalla-Favera
Summary: This study found that super-enhancers in the non-coding genome of DLBCL patients are highly mutated and linked to B cell developmental regulators and oncogenes. The mutations in these super-enhancers prevent the binding of transcriptional repressors and downregulation of target genes, indicating an oncogenic dependency. This research expands the involvement of known oncogenes in DLBCL pathogenesis and identifies new deregulated gene targets of therapeutic relevance.
Article
Biochemical Research Methods
Qi Wang, Zhaoqian Liu, Bo Yan, Wen-Chi Chou, Laurence Ettwiller, Qin Ma, Bingqiang Liu
Summary: ATUs in bacterial genomes are dynamically encoded under different conditions, with the computational framework SeqATU showing high accuracy in predicting ATUs in Escherichia coli based on RNA-Seq data, providing valuable insights into bacterial transcription mechanisms.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Computer Science, Information Systems
Jing Bi, Yongze Lin, Quanxi Dong, Haitao Yuan, MengChu Zhou
Summary: The study presents a hybrid model based on a neural network and a filter for water quality time series prediction, with experimental results demonstrating better predictive performance compared to other similar models.
INFORMATION SCIENCES
(2021)
Article
Plant Sciences
Boby Mathew, Andreas Hauptmann, Jens Leon, Mikko J. Sillanpaeae
Summary: Prediction of complex traits based on genome-wide marker information is crucial for animal and plant breeding. Many models have been proposed and efforts are being made to improve their accuracy, considering factors such as additive, dominance, and epistasis effects. In this study, a new algorithm that combines neural networks with LASSO is proposed, which accounts for local epistasis in the prediction. The new method was compared with commonly used prediction methods and showed superior accuracy.
FRONTIERS IN PLANT SCIENCE
(2022)
Review
Plant Sciences
Keiichi Mochdia, Shun Tamaki
Summary: The review highlights recent advances in gene discovery and functional analysis of transcription factors in microalgal species, emphasizing TF-based genetic engineering as a promising framework for designing microalgal strains for bioproduction.
Article
Biochemistry & Molecular Biology
Alan Garcia-Elfring, Christina E. Sabin, Anna L. Iouchmanov, Heather L. Roffey, Sukhada P. Samudra, Aaron J. Alcala, Rida S. Osman, James D. Lauderdale, Andrew P. Hendry, Douglas B. Menke, Rowan D. H. Barrett
Summary: Reptiles, such as ball pythons, exhibit a wide range of color and pattern variations. However, the genetic basis of coloration in reptiles is still poorly understood compared to model species like mice and zebrafish. In this study, researchers discovered a nonsense mutation in the tfec gene, which is responsible for the leucodermic patches in ball pythons. Functional validation of tfec in a lizard model showed that mutations in tfec affect coloration and iridophore development. This study highlights the importance of captive-bred ball pythons as a model species for understanding the genetic basis of vertebrate coloration.
Article
Biochemistry & Molecular Biology
Xiaoyue Luan, Wenlin Xu, Jiaqi Zhang, Tengfei Shen, Caihui Chen, Mengli Xi, Yongda Zhong, Meng Xu
Summary: This study systematically analyzed CcMYBs in C. camphora and identified 121 CcMYB genes. It was found that CcMYBs play various roles in the development of the camphor tree, and some of them may be related to flavonoid biosynthesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Radek Jankele, Rob Jelier, Pierre Goenczy
Summary: In the early embryonic development of C. elegans, unequal first cleavage is essential for successful development, as equalizing sizes results in defects in cell lineage, cell cycle progression, cell positioning, division orientation, and cell fate. Additionally, equalized embryos are more susceptible to external compression.
Article
Biology
Mireia Seuma, Andre J. Faure, Marta Badia, Ben Lehner, Benedetta Bolognesi
Summary: This study utilized deep mutational scanning to quantify the effects of mutations on the aggregation of A beta, providing mechanistic insights into fibril nucleation and highlighting the importance of charge and gatekeeper residues. Empirical nucleation scores accurately identified all known dominant fAD mutations in A beta, genetically validating similarities between nucleation mechanisms in cell-based assays and those causing the human disease, thus offering a comprehensive atlas of how mutations alter the formation of any amyloid fibril and aiding in the interpretation of genetic variation in A beta.
Article
Biochemical Research Methods
Wim Thiels, Bart Smeets, Maxim Cuvelier, Francesca Caroti, Rob Jelier
Summary: The study introduces an image analysis framework for automated tracking and segmentation of 3D cell shapes, utilizing sphere clustering and discrete element method simulation. Cellular geometries of Caenorhabditis elegans embryos are analyzed in various early stages, focusing on the 7- and 8-cell stage embryo geometry in terms of volume, contact area, and shape over time.
Article
Biochemistry & Molecular Biology
Marcos Francisco Perez, Mehrnaz Shamalnasab, Alejandro Mata-Cabana, Simona Della Valle, Maria Olmedo, Mirko Francesconi, Ben Lehner
Summary: Research shows that chemical pheromones in the social environment can be transmitted across generations through sensory neurons, significantly impacting the timing of offspring development.
Article
Cell Biology
Francesca Caroti, Wim Thiels, Michiel Vanslambrouck, Rob Jelier
Summary: During asymmetrical division of the endomesodermal precursor cell EMS, a cortical flow arises, leading to enduring differences in cell shape, tension, and movement between the daughter cells, potentially regulated by the Wnt signaling pathway.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Andre J. Faure, Julia Domingo, Jorn M. Schmiedel, Cristina Hidalgo-Carcedo, Guillaume Diss, Ben Lehner
Summary: This paper presents a method for globally mapping protein allostery using deep mutational scanning. The approach is applied to two common protein interaction domains in humans, revealing that mutations closer to binding interfaces, at specific residues, and at residues connecting to an opposite surface within the domain are more likely to be allosteric.
Article
Biochemical Research Methods
Romain Bulteau, Mirko Francesconi
Summary: RAPToR is a computational method based on transcriptomic data that precisely estimates the real age of a specimen. It can remove age as a confounding variable and recover the signal of interest in differential expression analysis.
Article
Multidisciplinary Sciences
Mischan Vali-Pour, Ben Lehner, Fran Supek
Summary: Somatic mutations play a crucial role in aging and cancer, with rare inherited variants potentially influencing mutational processes. Specific genes are associated with different forms of DNA repair deficiencies, and interactions between genes in cellular sub-networks are common. Damaging variants in newly-identified genes are prevalent in the population, highlighting the impact of germline variants on somatic mutations in cancer.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Mireia Seuma, Ben Lehner, Benedetta Bolognesi
Summary: This study generates a comprehensive atlas of variant effects for the amyloid beta peptide using deep indel mutagenesis. The results show that many substitutions can accelerate A beta aggregation and are likely to be pathogenic. Different classes of mutations have varying effects on aggregation, but likely pathogenic variants are highly enriched in the polar N-terminal region of A beta.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Casper van Bavel, Wim Thiels, Rob Jelier
Summary: The shape of a cell is important for understanding various cellular processes, but current cell shape descriptors only capture simple geometric features. This study proposes a new framework called FlowShape, which represents cell shape by measuring curvature and mapping it onto a sphere. The framework allows for various shape analyses, including alignment and statistical comparison.
Article
Biophysics
Maxim Cuvelier, Jef Vangheel, Wim Thiels, Herman Ramon, Rob Jelier, Bart Smeets
Summary: Cell division during early embryogenesis is influenced by the mechanical and geometrical environment, and this study presents a computational model that can accurately predict the volume ratio of daughter cells during the cleavage phase of development. The model also demonstrates how the orientation of confinement relative to the division axis and the properties of the cell cortex affect cell division and shape. Additionally, the model suggests that compression can affect spindle positioning and cell volume in asymmetric cell divisions.
BIOPHYSICAL JOURNAL
(2023)
Article
Biology
Ellen Geens, Pieter Van de Walle, Francesca Caroti, Rob Jelier, Christian Steuwe, Liliane Schoofs, Liesbet Temmerman
Summary: Oviparous animals support reproduction with yolk as a nutrient source. However, in Caenorhabditis elegans, yolk proteins don't affect fecundity, despite being the majority of embryonic protein pool and carriers for nutrient-rich lipids. Yolk provisioning in C. elegans provides temporal advantage during embryogenesis, increases early juvenile body size, and promotes competitive fitness. Unlike other species, C. elegans relies on yolk as a fail-safe for offspring survival rather than maintaining offspring numbers.
LIFE SCIENCE ALLIANCE
(2023)
Article
Multidisciplinary Sciences
Taylor Mighell, Ignasi Toledano, Ben Lehner
Summary: Multiplexed assays of variant effects (MAVEs) have enabled the functional assessment of all possible mutations to genes and regulatory sequences. However, current methods for generating variant libraries are either difficult to scale or lack uniformity. To address these limitations, we introduce a method called Scalable and Uniform Nicking (SUNi) mutagenesis, which allows cost-effective MAVEs of gene families and genomes with massive scalability and high uniformity.
Correction
Multidisciplinary Sciences
Mischan Vali-Pour, Solip Park, Jose Espinosa-Carrasco, Daniel Ortiz-Martinez, Ben Lehner, Fran Supek
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Xuan Xie, Xia Sun, Yuheng Wang, Ben Lehner, Xianghua Li
Summary: This article discusses how mutations interact to alter phenotypes and concludes that non-additive interactions (epistasis and dominance) are frequent, context-dependent, and challenging to predict even in the simplest biological systems.
NATURE COMMUNICATIONS
(2023)