New Phytol. 2025 Jan 31. doi: 10.1111/nph.20398. Online ahead of print.

ABSTRACT

HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE 15 (HOS15) acts as a substrate receptor of E3 ligase complex, which plays a negative role in drought stress tolerance. However, whether and how HOS15 participates in controlling important transcriptional regulators remains largely unknown. Here, we report that HOS15 physically interacts with and tightly regulates DROUGHT-INDUCED LIKE 19 (DIL9) protein stability. Moreover, application of exogenous abscisic acid (ABA) stabilizes the interaction between DIL9 and HOS15, leading to ABA-induced proteasomal degradation of DIL9 by HOS15. Genetic analysis revealed that DIL9 functions downstream to HOS15 and that the drought tolerance of hos15-2 plants was impaired in dil9/hos15 double mutants. Notably, DIL9 is directly associated with the promoter regions of ABF transcription factors and facilitates their expression, which is pivotal in enhancing ABA-dependent drought tolerance. Collectively, these findings demonstrate that HOS15 consistently degrades DIL9 under normal condition, while stress (drought/ABA) promotes the DIL9 activity for binding to the promoter regions of ABFs and positively regulates their expression in response to dehydration.

PMID:39888052 | DOI:10.1111/nph.20398

J Fish Dis. 2025 Jan 31:e14093. doi: 10.1111/jfd.14093. Online ahead of print.

ABSTRACT

White tail disease in Macrobrachium rosenbergii is caused by M. rosenbergii nodavirus (MrNV) infection, resulting in up to 100% mortality in larvae and post-larvae stages, severely impacting aquaculture production. Existing genome-based detection methods for MrNV are costly and time-consuming, highlighting the need for rapid and cost-effective diagnostic tests. This study evaluated the effects of truncating selected aptamer on its binding affinity to the MrNV capsid protein. The previously isolated and identified aptamer through magnetic-capture SELEX and Next Generation Sequencing demonstrated high binding affinity to the MrNV capsid protein. Truncation at the primer overhang was found to improve binding affinity, reducing the dissociation constant from 347 nM to 30.1 nM. The calculated limit of detection for the truncated aptamer decreased from 5.64 nM to 1.7 nM, while the limit of quantification decreased from 17.1 nM to 5.16 nM. These reductions indicate that the truncated aptamer has higher sensitivity compared to the full-length aptamer. In tests with MrNV-infected M. rosenbergii samples, both the enzyme-linked aptamer assay and the gold nanoparticle aptasensor assay showed consistent results when 0.5 μg of total protein lysate was used. This indicates that the prawn protein concentration interferes with the detection of the viral protein. These findings suggest the potential application of the truncated aptamer as a sensor in the development of a practical aptamer-based diagnostic kit. For instance, an aptamer-based lateral flow assay test kit could provide a user-friendly, cost-effective solution that eliminates the need for sophisticated instrumentation for diagnosis or data interpretation, making it ideal for detecting MrNV infection in M. rosenbergii aquaculture.

PMID:39887434 | DOI:10.1111/jfd.14093

Nat Commun. 2025 Jan 30;16(1):1176. doi: 10.1038/s41467-025-56303-0.

ABSTRACT

A protein's molecular interactions and post-translational modifications (PTMs), such as phosphorylation, can be co-dependent and reciprocally co-regulate each other. Although this interplay is central for many biological processes, a systematic method to simultaneously study assembly states and PTMs from the same sample is critically missing. Here, we introduce SEC-MX (Size Exclusion Chromatography fractions MultipleXed), a global quantitative method combining Size Exclusion Chromatography and PTM-enrichment for simultaneous characterization of PTMs and assembly states. SEC-MX enhances throughput, allows phosphopeptide enrichment, and facilitates quantitative differential comparisons between biological conditions. Conducting SEC-MX on HEK293 and HCT116 cells, we generate a proof-of-concept dataset, mapping thousands of phosphopeptides and their assembly states. Our analysis reveals intricate relationships between phosphorylation events and assembly states and generates testable hypotheses for follow-up studies. Overall, we establish SEC-MX as a valuable tool for exploring protein functions and regulation beyond abundance changes.

PMID:39885126 | DOI:10.1038/s41467-025-56303-0

Nat Commun. 2025 Jan 30;16(1):1182. doi: 10.1038/s41467-025-56449-x.

ABSTRACT

Ruminococcus gnavus is a gut bacterium found in > 90% of healthy individuals, but its increased abundance is also associated with chronic inflammatory diseases, particularly Crohn's disease. Nevertheless, its global distribution and intraspecies genomic variation remain understudied. By surveying 12,791 gut metagenomes, we recapitulated known associations with metabolic diseases and inflammatory bowel disease. We uncovered a higher prevalence and abundance of R. gnavus in Westernized populations and observed bacterial relative abundances up to 83% in newborns. Next, we built a resource of R. gnavus isolates (N = 45) from healthy individuals and Crohn's disease patients and generated complete R. gnavus genomes using PacBio circular consensus sequencing. Analysis of these genomes and publicly available high-quality draft genomes (N = 333 genomes) revealed multiple clades which separated Crohn's-derived isolates from healthy-derived isolates. Presumed R. gnavus virulence factors could not explain this separation. Bacterial genome-wide association study revealed that Crohn's-derived isolates were enriched in genes related to mobile elements and mucin foraging. Together, we present a large R. gnavus resource that will be available to the scientific community and provide novel biological insights into the global distribution and genomic variation of R. gnavus.

PMID:39885121 | DOI:10.1038/s41467-025-56449-x

Plant Cell Rep. 2025 Jan 30;44(2):46. doi: 10.1007/s00299-025-03432-x.

ABSTRACT

Twenty-nine GRAS genes were identified in passion fruit, the N-terminal regions and 3D (three-dimensional) structures were closely related with their tissue-specific expression patterns. Candidate PeGRASs for enhancing stress resistance were identified. Passion fruit (Passiflora edulis Sims) is a tropical fruit crop with significant edible and ornamental value, but its growth and development are highly sensitive to environmental conditions. The plant-specific GRAS gene family plays critical roles in regulating growth, development, and stress responses. Here, we performed the first comprehensive analysis of the GRAS gene family in passion fruit. A total of 29 GRAS genes were identified and named PeGRAS1 to PeGRAS29 based on their chromosomal locations. Phylogenetic analysis using GRAS proteins from passion fruit, Arabidopsis, and rice revealed that PeGRAS proteins could be classified into 10 subfamilies. Compared to Arabidopsis, passion fruit lacked members from the LAS subfamily but gained one GRAS member (PeGRAS9) clustered with the rice-specific Os4 subfamily. Structural analysis performed in silico revealed that most PeGRAS members were intron less and exhibited conserved motif patterns near the C-terminus, while the N-terminal regions varied in sequence length and composition. Members within certain subfamilies including DLT, PAT1, and LISCL with similar unstructured N-terminal regions and 3D structures, exhibited similar tissue-specific expression patterns. While PeGRAS members with difference in these structural features, even within the same subfamily (e.g., DELLA), displayed distinct expression patterns. These findings highlighted that the N-terminal regions of GRAS proteins may be critical for their specific functions. Moreover, many PeGRAS members, particularly those from the PAT1 subfamily, were widely involved in stress responses, with PeGRAS19 and PeGRAS26 likely playing roles in cold tolerance, and PeGRAS25 and PeGRAS28 in drought resistance. This study provides a foundation for further functional research on PeGRASs and offers potential candidates for molecular breeding aimed at enhancing stress tolerance in passion fruit.

PMID:39885065 | DOI:10.1007/s00299-025-03432-x

Methods Mol Biol. 2025;2895:3-13. doi: 10.1007/978-1-0716-4350-1_1.

ABSTRACT

This introductory chapter traces the evolution of (bio)chemical assays, emphasizing the critical role of robust protocols in ensuring reproducibility-a fundamental aspect of scientific research. With the advent of systems biology, the need for standardized methods has intensified, particularly for integrating vast datasets in open-access formats. The historical progression from basic plant morphology to advanced chromatographic and spectroscopic techniques in phytochemistry highlights the necessity for precise, reproducible protocols.As metabolomics advances, there is a renewed focus on targeted approaches, shifting from broad, untargeted analyses to more specific, hypothesis-driven studies. This chapter also explores the future of analytical techniques, including cellomics and real-time metabolic flux measurements, which offer new insights into dynamic biochemical processes.Ultimately, this introduction underscores the importance of innovation in developing new methods that address current scientific challenges, particularly in pharmacognosy and analytical phytochemistry. The chapter sets the stage for the broader discussion on the necessity of well-designed protocols that facilitate effective data sharing and collaboration across research disciplines.

PMID:39885019 | DOI:10.1007/978-1-0716-4350-1_1

J Mol Biol. 2025 Jan 28:168961. doi: 10.1016/j.jmb.2025.168961. Online ahead of print.

ABSTRACT

N4-acetylcytidine (ac4C) is a crucial post-transcriptional modification in human mRNA, involving the acetylation of the nitrogen atom at the fourth position of cytidine. This modification, catalyzed by N-acetyltransferases such as NAT10, is primarily found in mRNA's coding regions and enhances translation efficiency and mRNA stability. ac4C is closely associated with various diseases, including cancer. Therefore, accurately identifying ac4C in human mRNA is essential for gaining deeper insights into disease pathogenesis and provides potential pathways for the development of novel medical interventions. In silico methods for identifying ac4C are gaining increasing attention due to their cost-effectiveness, requiring minimal human and material resources. In this study, we propose an efficient and accurate computational framework, Caps-ac4C, for the precise detection of ac4C in human mRNA. Caps-ac4C utilizes chaos game representation to encode RNA sequences into "images" and employs capsule networks to learn global and local features from these RNA "images". Experimental results demonstrate that Caps-ac4C achieves state-of-the-art performance, achieving 95.47% accuracy and 0.912 MCC on the test set, surpassing the current best methods by 10.69% accuracy and 0.216 MCC. In summary, Caps-ac4C represents the most accurate tool for predicting ac4C sites in human mRNA, highlighting its significant contribution to RNA modification research. For user convenience, we developed a user-friendly web server, which can be accessed for free at:https://awi.cuhk.edu.cn/Caps-ac4C/index.php.

PMID:39884569 | DOI:10.1016/j.jmb.2025.168961

Virol Sin. 2025 Jan 28:S1995-820X(25)00004-5. doi: 10.1016/j.virs.2025.01.004. Online ahead of print.

NO ABSTRACT

PMID:39884360 | DOI:10.1016/j.virs.2025.01.004

Structure. 2025 Jan 21:S0969-2126(25)00002-4. doi: 10.1016/j.str.2025.01.002. Online ahead of print.

ABSTRACT

Broadly neutralizing antibodies (nAbs) are vital therapeutic tools to counteract both pandemic and seasonal influenza threats. Traditional strategies for optimizing nAbs generally rely on labor-intensive, high-throughput mutagenesis screens. Here, we present an innovative structure-based design framework for the optimization of nAbs, which integrates epitope-paratope analysis, computational modeling, and rational design approaches, complemented by comprehensive experimental assessment. This approach was applied to optimize MEDI8852, a nAb targeting the stalk region of influenza A virus hemagglutinin (HA). The resulting variant, M18.1.2.2, shows a marked enhancement in both affinity and neutralizing efficacy, as demonstrated both in vitro and in vivo. Computational modeling reveals that this improvement can be attributed to the fine-tuning of interactions between the antibody's side-chains and the epitope residues that are highly conserved across the influenza A virus HA stalk. Our dry-wet iterative protocol for nAb optimization presented here yielded a promising candidate for influenza intervention.

PMID:39884272 | DOI:10.1016/j.str.2025.01.002

Talanta. 2025 Jan 23;287:127619. doi: 10.1016/j.talanta.2025.127619. Online ahead of print.

ABSTRACT

Cysteamine (CA) serves as a cystine-depleting agent employed in the management of cystinosis and a range of other medical conditions. Monitoring blood CA levels at the point of care is imperative due to the risk of toxicity associated with elevated CA dosages. An additional significant challenge is presented by the intricate composition of human plasma and the presence of various interfering biological thiols, which possess similar structures or properties. Here, this work proposes an AI-enhanced Lab-on-a-disc system, also termed AI-LOAD, for multiplexed point-of-care testing of cysteamine. The AI-LOAD system incorporates an online whole blood separation mechanism alongside a naked-eye colorimetric detection module, facilitating the rapid and precise visual identification of cysteamine. Remarkably, the system necessitates only 40 μL of whole blood to analyze eight samples within 3-min, achieving a limit of detection as low as 10 μM, which is lower than the physiological toxic concentration of 0.1 mM. By leveraging diverse colorimetric responses generated through interactions between gold nanoparticles of varying sizes and different biological thiols, combined with artificial intelligence methodologies, the system successfully accomplished specific recognition of various biological thiols with 100 % accuracy. The proposed AI-LOAD will drive advancements in centrifugal microfluidics for point-of-care testing, thereby holding potential for broader applications in future biomedical research and in vitro diagnosis.

PMID:39884122 | DOI:10.1016/j.talanta.2025.127619

ACS Synth Biol. 2025 Jan 30. doi: 10.1021/acssynbio.4c00672. Online ahead of print.

ABSTRACT

Fungi, especially filamentous fungi, are a relatively understudied, biotechnologically useful resource with incredible potential for commercial applications. These multicellular eukaryotic organisms have long been exploited for their natural production of useful commodity chemicals and proteins such as enzymes used in starch processing, detergents, food and feed production, pulping and paper making and biofuels production. The ability of filamentous fungi to use a wide range of feedstocks is another key advantage. As chassis organisms, filamentous fungi can express cellular machinery, and metabolic and signal transduction pathways from both prokaryotic and eukaryotic origins. Their genomes abound with novel genetic elements and metabolic processes that can be harnessed for biotechnology applications. Synthetic biology tools are becoming inexpensive, modular, and expansive while systems biology is beginning to provide the level of understanding required to design increasingly complex synthetic systems. This review covers the challenges of working in filamentous fungi and offers a perspective on the approaches needed to exploit fungi as microbial cell factories.

PMID:39883596 | DOI:10.1021/acssynbio.4c00672

PLoS Biol. 2025 Jan 30;23(1):e3002730. doi: 10.1371/journal.pbio.3002730. eCollection 2025 Jan.

ABSTRACT

Food presents a multisensory experience, with visual, taste, and olfactory cues being important in allowing an animal to determine the safety and nutritional value of a given substance. Texture, however, remains a surprisingly unexplored aspect, despite providing key information about the state of the food through properties such as hardness, liquidity, and granularity. Food perception is achieved by specialised sensory neurons, which themselves are defined by the receptor genes they express. While it was assumed that sensory neurons respond to one or few closely related stimuli, more recent findings challenge this notion and support evidence that certain sensory neurons are more broadly tuned. In the Drosophila taste system, gustatory neurons respond to cues of opposing hedonic valence or to olfactory cues. Here, we identified that larvae ingest and navigate towards specific food substrate hardnesses and probed the role of gustatory organs in this behaviour. By developing a genetic tool targeting specifically gustatory organs, we show that these organs are major contributors for evaluation of food hardness and ingestion decision-making. We find that ablation of gustatory organs not only results in loss of chemosensation, but also navigation and ingestion preference to varied substrate hardnesses. Furthermore, we show that certain neurons in the primary taste organ exhibit varied and concurrent physiological responses to mechanical and multimodal stimulation. We show that individual neurons house independent mechanisms for multiple sensory modalities, challenging assumptions about capabilities of sensory neurons. We propose that further investigations, across the animal kingdom, may reveal higher sensory complexity than currently anticipated.

PMID:39883595 | DOI:10.1371/journal.pbio.3002730

Tree Physiol. 2025 Jan 30:tpaf016. doi: 10.1093/treephys/tpaf016. Online ahead of print.

ABSTRACT

Ink disease caused by the hemibiotrophic root pathogen Phytophthora cinnamomi (Pc) is devastating for the European chestnut (Castanea sativa), unlike Asian chestnuts and interspecific hybrids which are resistant to Pc. The role that hormone responses play for Pc resistance remains little understood, especially regarding the temporal regulation of hormone responses. We explored the relationship between changes in tree health and physiology and alterations in leaf and root phytohormones and primary and secondary metabolites during compatible and incompatible Castanea spp.-Pc interactions. Susceptible (S) C. sativa and resistant (R) C. sativa x C. crenata ramets were inoculated with Pc in roots and assessed for disease progression, leaf physiology and biochemistry at 1, 3, 5 and 8 days after inoculation (dai). In S chestnuts, Pc increasingly deteriorated the leaf physiological functioning by decreasing leaf CO2 assimilation, stomatal conductance, transpiration rate, chlorophylls content and the maximum quantum yield of the photosystem II over time, triggering aerial symptoms (leaf wilting and chlorosis) 8 dai. Pc had little impact on the leaf physiological functioning of R chestnuts which remained asymptomatic. In roots of S chestnuts, Pc transiently induced jasmonates signaling (5 dai) while impairing root carbohydrates metabolism over time. In leaves, a transient antioxidant burst (5 dai) followed by abscisic acid (ABA) accumulation (8 dai) was observed. R chestnuts responded to Pc by up-regulating root salicylic acid (SA) at early (1 dai) and late (8 dai) infection stages, in an antagonistic crosstalk with root ABA. Overall, the results pinpoint an important role of SA in mediating the resistant response of chestnuts to Pc, but also show that the specific hormone pathways induced by Pc are genotype dependent. The study also highlights that the dynamic nature of hormone responses over time must be considered when elucidating hormone-regulated responses to Pc.

PMID:39883087 | DOI:10.1093/treephys/tpaf016

J R Soc Interface. 2025 Jan;22(222):20240404. doi: 10.1098/rsif.2024.0404. Epub 2025 Jan 30.

ABSTRACT

Bond graphs provide an energy-based methodology for modelling complex systems hierarchically; at the moment, the method allows biological systems with both chemical and electrical subsystems to be modelled. Herein, the bond graph approach is extended to include chemomechanical transduction thus extending the range of biological systems to be modelled. Actin filament polymerization and force generation is used as an example of chemomechanical transduction, and it is shown that the TF (transformer) bond graph component provides a practical, and conceptually simple, alternative to the Brownian ratchet approach of Peskin, Odell, Oster and Mogilner. Furthermore, it is shown that the bond graph approach leads to the same equation as the Brownian ratchet approach in the simplest case. The approach is illustrated by showing that flexibility and non-normal incidence can be modelled by simply adding additional bond graph components and that compliance leads to non-convexity of the force-velocity curve. Energy flows are fundamental to life; for this reason, the energy-based approach is utilized to investigate the power transmission by the actin filament and its corresponding efficiency. The bond graph model is fitted to experimental data by adjusting the model physical parameters.

PMID:39881657 | DOI:10.1098/rsif.2024.0404

Environ Toxicol Chem. 2025 Jan 28:vgaf028. doi: 10.1093/etojnl/vgaf028. Online ahead of print.

ABSTRACT

Given the need to reduce animal testing for environmental risk assessment, we aim to develop a fish invitrome, an alternative fish modular framework capable of predicting chemical toxicity in fish without the use of animals. The central module of the framework is the validated RTgill-W1 cell line assay that predicts fish acute toxicity of chemicals (Organization for Economic Cooperation and Development Test Guideline (OECD TG) 249). Expanding towards prediction of chronic toxicity, the fish invitrome includes two other well-advanced modules for chemical bioaccumulation/biotransformation and inhibition of fish growth. This framework is expected to continuously evolve with the development of modules that predict, for instance, neurotoxicity and reproductive toxicity. We envisage the fish invitrome framework to become part of the broader academic field of New Approach Methodologies (NAMs), where it will remain flexible and open to integration of new developments from research groups around the world. To accelerate the development and uptake of this framework, we strive for transdisciplinarity, integrating both natural and social sciences, along with broader stakeholder interactions. A stepwise socio-technical approach has been chosen, where mainstreaming the fish invitrome involves progressive adoption across various ecotoxicological contexts. The framework will be co-designed with stakeholders from academia, industry, and regulatory bodies. Rather than aiming for immediate regulatory acceptance, this approach aims to build trust and familiarity with fish cell line-based testing among stakeholders. By doing so, it encourages broader use of the framework in practical applications while gradually overcoming institutional, cultural, and technical barriers. Additionally, establishing a clear roadmap for mainstreaming the fish invitrome will help identify and address challenges to its uptake, ensuring a smoother transition to non-organismal testing methodologies.

PMID:39880375 | DOI:10.1093/etojnl/vgaf028

Biochim Biophys Acta Gen Subj. 2025 Jan 27:130768. doi: 10.1016/j.bbagen.2025.130768. Online ahead of print.

ABSTRACT

Apolipoprotein E (apoE) polymorphism is associated with different pathologies such as atherosclerosis and Alzheimer's disease. Knowledge of the three-dimensional structure of apoE and isoform-specific structural differences are prerequisites for the rational design of small molecule structure modulators that correct the detrimental effects of pathological isoforms. In this study, cross-linking mass spectrometry (XL-MS) targeting Asp, Glu and Lys residues was used to explore the intramolecular interactions in the E2, E3 and E4 isoforms of apoE. The resulting quantitative XL-MS data combined with molecular modeling revealed isoform-specific characteristics of the N- and C-terminal domain interfaces as well as the isoform-dependent dynamic equilibrium of these interfaces. Finally, the data identified a network of salt bridges formed by R61-R112-E109 residues in the N-terminal helical bundle as a modulator of the interaction with the C-terminal domain making this network a potential drug target.

PMID:39880049 | DOI:10.1016/j.bbagen.2025.130768

Curr Biol. 2025 Jan 23:S0960-9822(24)01707-X. doi: 10.1016/j.cub.2024.12.039. Online ahead of print.

ABSTRACT

Yeasts are a diverse group of unicellular fungi that have developed a wide array of phenotypes and traits over 400 million years of evolution. However, we still lack an understanding of the biological principles governing the range of cell morphologies, metabolic modes, and reproductive strategies yeasts display. In this study, we explored the relationship between cell morphology and metabolism in sixteen yeast strains across eleven species. We performed a quantitative analysis of the physiology and morphology of these strains and discovered a strong correlation between the glucose uptake rate (GUR) and the surface-area-to-volume ratio. 14C-glucose uptake experiments demonstrated that the GUR for a given strain is governed either by glucose transport capacity or glycolytic rate, indicating that it is rather the rate of glucose metabolism in general that correlates with cell morphology. Furthermore, perturbations in glucose metabolism influenced cell sizes, whereas manipulating cell size did not affect GUR, suggesting that glucose metabolism determines cell size rather than the reverse. Across the strains tested, we also found that the rate of glucose metabolism influenced ethanol production rate, biomass yield, and carbon dioxide transfer rate. Overall, our findings demonstrate that the rate of glucose metabolism is a key factor shaping yeast cell morphology and physiology, offering new insights into the fundamental principles of yeast biology.

PMID:39879976 | DOI:10.1016/j.cub.2024.12.039

Mar Pollut Bull. 2025 Jan 28;212:117615. doi: 10.1016/j.marpolbul.2025.117615. Online ahead of print.

ABSTRACT

The Strait of Sicily, a vital marine passage with diverse fauna, is seeing a steep rise in the planning of offshore wind farm projects. This study assesses the acoustic impact of these wind farms on local marine species. Underwater propagation was modeled for three proposed floating wind farms using JASCO's Marine Operations Noise Model (MONM), which integrates a parabolic equation method for frequencies from 10 to 800 Hz and a beam-tracing model for 1 to 25 kHz. Propagation losses were calculated in one-third octave bands for ten source locations selected to represent the variability in bathymetry, and considering sound speed profiles for February and August. Sound levels from floating turbines were used to estimate exceedance ranges to known acoustic thresholds for marine species. Modeling indicated that sound levels could exceed temporary threshold shift and, for some species, permanent threshold shift criteria within a few tens of meters, but only if animals were to remain for 24 h at such small distances from a turbine. Behavioral disturbance thresholds for marine mammals were exceeded up to 68 km from the wind farms' boundaries. The study emphasizes considering species-specific sensitivities and ecological contexts in environmental impact assessments, recommending mitigation measures, such as the strategic placement of the turbines and continuous monitoring, to minimize adverse effects on local marine fauna, including marine mammals and turtles.

PMID:39879849 | DOI:10.1016/j.marpolbul.2025.117615

Stem Cell Res. 2025 Jan 15;83:103660. doi: 10.1016/j.scr.2025.103660. Online ahead of print.

ABSTRACT

NHD/PLOSL is an orphan disease characterized by progressive presenile dementia associated with recurrent fractures due to polycystic bone lesions. In this study, we generated the human induced pluripotent stem cell (hiPSC) line BIHi292-A from a 30-year-old women diagnosed with NHD/PLOSL, carrying two compound heterozygous frameshift mutations [c.313del (p.Ala105fs) and c.199del (p.His67fs)] in the TREM2 (triggering receptor expressed on myeloid cells 2) gene. BIHi292-A hiPSCs are karyotypically normal, express typical markers for the undifferentiated state and have pluripotent differentiation potential. BIHi292-A cells will provide a valuable tool for investigating pathogenic mechanisms of NHD/PLOSL and TREM2-related research questions.

PMID:39879812 | DOI:10.1016/j.scr.2025.103660

Brief Bioinform. 2024 Nov 22;26(1):bbaf039. doi: 10.1093/bib/bbaf039.

ABSTRACT

Pathway analysis plays a critical role in bioinformatics, enabling researchers to identify biological pathways associated with various conditions by analyzing gene expression data. However, the rise of large, multi-center datasets has highlighted limitations in traditional methods like Over-Representation Analysis (ORA) and Functional Class Scoring (FCS), which struggle with low signal-to-noise ratios (SNR) and large sample sizes. To tackle these challenges, we use a deep learning-based classification method, Gene PointNet, and a novel $P$-value computation approach leveraging the confusion matrix to address pathway analysis tasks. We validated our method effectiveness through a comparative study using a simulated dataset and RNA-Seq data from The Cancer Genome Atlas breast cancer dataset. Our method was benchmarked against traditional techniques (ORA, FCS), shallow machine learning models (logistic regression, support vector machine), and deep learning approaches (DeepHisCom, PASNet). The results demonstrate that GPNet outperforms these methods in low-SNR, large-sample datasets, where it remains robust and reliable, significantly reducing both Type I error and improving power. This makes our method well suited for pathway analysis in large, multi-center studies. The code can be found at https://github.com/haolu123/GPNet_pathway">https://github.com/haolu123/GPNet_pathway.

PMID:39879387 | DOI:10.1093/bib/bbaf039