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http://dx.doi.org/10.1371/journal.pcbi.1002285 | DOI Listing |
J Chem Inf Model
September 2025
College of Agriculture and Biological Science, Dali University, Dali 671000, China.
The E76K mutation in protein tyrosine phosphatase (PTP) SHP2 is a recurrent driver of developmental disorders and cancers, yet the mechanism by which this single-site substitution promotes persistent activation remains elusive. Here, we combine path-based conformational sampling, unbiased molecular dynamics (MD) simulations, Markov state models (MSMs), and neural relational inference (NRI) to elucidate how E76K reshapes the activation landscape and regulatory architecture of SHP2. Using a minimum-action trajectory derived from experimentally determined closed and open structures, we generated representative transition intermediates to guide the unbiased MD simulations.
View Article and Find Full Text PDFPLoS Comput Biol
September 2025
Department of Mathematical and Computational Methods, National Laboratory for Scientific Computing, Petrópolis, Brazil.
Understanding cerebral circulation is crucial for early diagnosis and patient-oriented therapies for brain conditions. However, blood flow simulations at the organ scale have been limited. This work introduces a framework for modeling extensive vascular networks in the human cerebral cortex and conducting pulsatile blood flow simulations.
View Article and Find Full Text PDFPLoS Comput Biol
September 2025
OmnibusXLab, OmnibusX Company Limited, Ho Chi Minh City, Vietnam.
OmnibusX is an integrated, privacy-centric platform that enables code-free multi-omics data analysis by bridging computational methodologies with user-friendly interfaces. Designed to overcome challenges posed by fragmented analytical tools and high computational barriers, OmnibusX consolidates workflows for diverse technologies - including bulk RNA-seq, single-cell RNA-seq, single-cell ATAC-seq, and spatial transcriptomics - into a single, cohesive application. The application integrates established open-source tools such as Scanpy, DESeq2, SciPy, and scikit-learn into transparent, reproducible pipelines, offering users control over analytical parameters.
View Article and Find Full Text PDFPLoS Comput Biol
September 2025
Mathematical and Statistical Methods (Biometris), Wageningen University, Wageningen, The Netherlands.
Many plant cell functions, including cell morphogenesis and anisotropic growth, rely on the self-organisation of cortical microtubules into aligned arrays with the correct orientation. An important ongoing debate is how cell geometry, wall mechanical stresses, and other internal and external cues are integrated to determine the orientation of the cortical array. Here, we demonstrate that microtubule-based nucleation can markedly shift the balance between these often competing directional cues.
View Article and Find Full Text PDFPLoS One
September 2025
Smart Manufacturing and Artificial Intelligence, Micron Memory Malaysia Sdn. Bhd., Batu Kawan, Penang, Malaysia.
Advances in data collection have resulted in an exponential growth of high-dimensional microarray datasets for binary classification in bioinformatics and medical diagnostics. These datasets generally possess many features but relatively few samples, resulting in challenges associated with the "curse of dimensionality", such as feature redundancy and an elevated risk of overfitting. While traditional feature selection approaches, such as filter-based and wrapper-based approaches, can help to reduce dimensionality, they often struggle to capture feature interactions while adequately preserving model generalization.
View Article and Find Full Text PDF