bluuebunny/crossref_metadata_2025_split huggingface dataset:
FastReseg: using transcript locations to refine image-based cell segmentation results in spatial transcriptomics
Authors: Wu Lidan , Beechem Joseph M. , Danaher Patrick 
Published: December 2024

AbstractSpatial transcriptomics (ST) is a rapidly advancing field, yet it is challenged by persistent issues with cell segmentation accuracy, which can bias biological interpretations by making cells appear more similar to their neighbors than they truly are. FastReseg introduces a novel class of algorithm that employs transcriptomic data not to redefine cell boundaries but to rectify inaccuracies within existing image-based segmentation outputs. By combining the rich information from image-based methods with the 3D precision of transcriptomic analysis, FastReseg enhances cell segmentation accuracy. A key innovation of FastReseg approach is its transcript scoring system, which scores each transcript for its goodness-of-fit within host cell using log-likelihood ratio. This scoring system facilitates the quick identification and correction of spatial doublets,i.e.cells erroneously segmented due to close proximity or spatial overlap in 2D. FastReseg approach offers several advantages: it reduces the risks of circularity in deriving cell boundaries from expression data and minimizes spatial-dependent biases arising from erroneous segmentation. It also addresses computational challenges often associated with existing transcript-based methods by introducing a heuristic, modular workflow that efficiently processes large datasets, a critical feature given the increasing size of spatial transcriptomics datasets. Its modular workflow allows for individual components to be optimized and seamlessly integrated back into the overall pipeline, accommodating ongoing advancements in segmentation technology. By enabling efficient management of large datasets and providing a scalable solution for refining cell segmentation, FastReseg is poised to enhance the quality and interpretability of spatial transcriptomics data even as underlying image-based cell segmentation techniques evolve.
In Search of Transcriptomic Correlates of Neuronal Firing-Rate Adaptation across Subtypes, Regions and Species: A Patch-seq Analysis
Authors: Meng John Hongyu , Kang Yijie , Lai Alan , Feyerabend Michael , Inoue Wataru , Martinez-Trujillo Julio , Rudy Bernardo , Wang Xiao-Jing 
Published: December 2024

AbstractCan the transcriptomic profile of a neuron predict its physiological properties? Using a Patch-seq dataset of the primary visual cortex, we addressed this question by focusing on spike rate adaptation (SRA), a well-known phenomenon that depends on small conductance calcium (Ca)-dependent potassium (SK) channels. We first show that in parvalbumin-expressing (PV) and somatostatin-expressing (SST) interneurons (INs), expression levels of genes encoding the ion channels underlying action potential generation are correlated with the half-width (HW) of spikes. Surprisingly, the SK encoding gene is not correlated with the degree of SRA (dAdap). Instead, genes that encode proteins upstream from the SK current are correlated with dAdap, a finding validated by a different dataset from the mouse’s primary motor cortex that includes pyramidal cells and interneurons, as well as physiological datasets from multiple regions of macaque monkeys. Finally, we construct a minimal model to reproduce observed heterogeneity across cells, with testable predictions.
Gabapentin’s Effect on Human Dorsal Root Ganglia: Donor-Specific Electrophysiological and Transcriptomic Profiles
Authors: Demeter Jenna B. , Zurek Nesia A. , Koch Maddy R. , Goins Aleyah E. , Holguin Cristian O. , Shilling Mark W. , Ehsanian Reza , Alles Sascha R.A. , de la Peña June Bryan I. 
Published: December 2024

AbstractNeuropathic pain affects approximately 10% of the adult population and is commonly treated with gabapentin (GBP), a repurposed anticonvulsant drug. Despite its widespread clinical use, GBP’s efficacy varies significantly among patients, highlighting the need to better understand its functional and molecular impacts on human pain-sensing neurons. In this study, we characterized the electrophysiological and transcriptomic effects of GBP on primary sensory neurons derived from the dorsal root ganglia (DRG) of ethically consented human donors. Using patch-clamp electrophysiology, we demonstrated that GBP treatment reduced neuronal excitability, with more pronounced effects in multi-firing vs. single-firing neuronal subtypes. Notably, significant donor-specific variability was observed in electrophysiological responsiveness to GBP treatmentin vitro. RNA sequencing of DRG tissue from the GBP-responsive donor revealed differences in the transcriptome-wide expression of genes associated with ion transport, synaptic transmission, inflammation, and immune response relative to non-responsive donors. Cross-transcriptomic analyses further showed that GBP treatment counteracted these altered processes, rescuing aberrant gene expression at the pathway level and for several key genes. This study provides a comprehensive electrophysiological and transcriptomic profile of the effects of GBP on human DRG neurons. These findings enhance our understanding of GBP’s mechanistic actions on peripheral sensory neurons and could help optimize its clinical use for neuropathic pain management.
An imbalance of naïve and effector T-cell phenotypes in early type 1 diabetes across conventional and regulatory subsets
Authors: Niederlova Veronika , Neuwirth Ales , Neuman Vit , Michalik Juraj , Charvatova Bela , Modrak Martin , Sumnik Zdenek , Stepanek Ondrej 
Published: December 2024

AbstractType 1 diabetes (T1D) is an autoimmune disease caused by the loss of self-tolerance toward insulin-producing pancreatic β-cells. Although the etiology of T1D is not fully understood, it is linked to dysregulation of the T-cell compartment. To identify T-cell signatures associated with T1D, we performed single-cell transcriptomic analysis of peripheral blood T-cells from newly diagnosed children, the same children after one year, and healthy donors. We observed reduced expression of genes related to effector and cytotoxic T-cell functions across conventional, unconventional, and regulatory T-cell subsets in diabetic children, particularly at the time of diagnosis. These findings were supported by flow cytometry analysis of the same cohort and by reanalysis of publicly available data. Overall, our results suggest that T1D is associated with impaired T-cell effector differentiation, which may contribute to immune dysregulation and loss of self-tolerance.
DiscoEPG: A Python package for characterization of insect electrical penetration graph (EPG) signals
Authors: Dinh Quang Dung , Kunk Daniel , Hy Truong Son , Vamsi Nalam , Dao Phuong D. 
Published: December 2024

AbstractThe Electrical Penetration Graph (EPG) technique is a well-known specialized tool that entomologists use to monitor and analyze the feeding behavior of piercing-sucking insects, such as aphids, whiteflies, and leafhoppers, on plants. Traditionally, the annotation is conducted by a well-trained technician who uses expert knowledge to compare the targeted waveforms with standard waveforms of aphid feeding behavior, which takes approximately 30 minutes to annotate an 8-hour recording depending on the complexity of the insect behaviors. Machine learning (ML) models, which shown great potential in monitoring insects behaviors, have recently been used to speed up this process. However, most publicly available tools that provide automatic annotation suffer from low prediction accuracy due to only using simple distinction rules to classify waveforms. For this reason, we developDiscoEPG, an open-source Python package which performs accurate automatic EPG signal annotation. Various ML algorithms were experimented rigorously, which reports greater prediction power and improved accuracy in comparison to previous studies. In addition, we equipped our package with novel tools for generating journal-level plots to facilitate visual inspection, while including the computation of various EPG parameters and necessary statistical analysis which are popular in the research of aphids. WithDiscoEPG, we aim to facilitate the rapid characterization of analysis of piercing-sucking insects feeding behavior through EPG signal, making this technique more viable to researchers who share the same interest. Our package is publicly available at:https://github.com/HySonLab/ML4Insects.
Defining a highly conserved B cell epitope in the receptor binding motif of SARS-CoV-2 spike glycoprotein
Authors: Malladi Sameer Kumar , Jaiswal Deepika , Ying Baoling , Alsoussi Wafaa B. , Darling Tamarand L. , Dadonaite Bernadeta , Civljak Alesandro , Horvath Stephen C. , Zhou Julian Q. , Kim Wooseob , Turner Jackson S. , Schmitz Aaron J. , Han Fangjie , Scheaffer Suzanne M. , Farnsworth Christopher W. , Nachbagauer Raffael , Nestorova Biliana , Chalkias Spyros , Klebert Michael K. , Edwards Darin K. , Paris Robert , Strnad Benjamin S. , Middleton William D. , O’Halloran Jane A. , Presti Rachel M. , Bloom Jesse D. , Boon Adrianus C. M. , Diamond Michael S. , Bajic Goran , Ellebedy Ali H. 
Published: December 2024

AbstractSARS-CoV-2 mRNA vaccines induce robust and persistent germinal centre (GC) B cell responses in humans. It remains unclear how the continuous evolution of the virus impacts the breadth of the induced GC B cell response. Using ultrasound-guided fine needle aspiration, we examined draining lymph nodes of nine healthy adults following bivalent booster immunization. We show that 77.8% of the B cell clones in the GC expressed as representative monoclonal antibodies recognized the spike protein, with a third (37.8%) of these targeting the receptor binding domain (RBD). Strikingly, only one RBD-targeting mAb, mAb-52, neutralized all tested SARS- CoV-2 strains, including the recent KP.2 variant. mAb-52 utilizes the IGHV3-66 public clonotype, protects hamsters challenged against the EG.5.1 variant and targets the class I/II RBD epitope, closely mimicking the binding footprint of ACE2. Finally, we show that the remarkable breadth of mAb-52 is due to the somatic hypermutations accumulated within vaccine-induced GC reaction.One Sentence SummaryBooster SARS-CoV-2 mRNA vaccine recruits and broadens GC B cell responses targeting a highly conserved site on receptor binding domain of spike glycoprotein.
Vocal species are more central in Eastern Himalayan Mixed-Species bird flocks
Authors: Gupta Satyam , Bharadwaj Akshay , Bhat Akshiti , Thapa Aiti , Biswakarma Aman , Tamang Bharat , Munda Binod , Biswakarma Biren , Tamang Dema , Pradhan Dambar , Rai Mangal K , Rai Rohit , Rai Shambh , Srinivasan Umesh 
Published: December 2024

ABSTRACTMixed-species flocks (MSF) represent an important form of social organisation in bird communities worldwide. Despite its likely importance in flock formation and cohesion, the role of vocal communication in the formation and maintenance of MSF in birds is hitherto understudied. In this study, we examine if a species’ centrality within a mixed-species flock is influenced by its vocal behaviour during the dawn chorus, i.e., the time of MSF formation. Using acoustic sampling and field observation, we studied bird species found in MSF in the Eastern Himalayas. Our results show differential vocal activity patterns among MSF-forming bird species and suggest a positive correlation between calling rates and closeness centrality in understory MSFs. We also found a more synchronised vocalisation pattern in the understory MSFs, with a consistent peak in vocal activity in the early morning hours, whereas no consistent vocal pattern was found for canopy flocks. Overall, our results suggest a potential mechanism that drives MSF formation wherein the vocal activity of central species precedes and likely attracts participation from other attendant species.
Multi-omic integration with human DRG proteomics highlights TNFα signalling as a relevant sexually dimorphic pathway
Authors: Barry Allison M , Sondermann Julia R , Lesnak Joseph B , Xian Feng , Franco-Enzástiga Úrzula , O’Brien Jayden A , Varela David Gomez , Schackmuth Morgan K , Shiers Stephanie , Price Theodore J , Schmidt Manuela 
Published: December 2024

AbstractThe peripheral nervous system has been widely implicated in pathological conditions that exhibit distinct clinical presentations in men and women, most notably in chronic pain disorders. Here, we explored this sexual dimorphism at a molecular level. We expanded the available omics landscape in the PNS to include quantitative proteomics of the human dorsal root ganglia (hDRG) and nerve. Using data-independent acquisition mass spectrometry, we uncovered an extensive protein landscape, validated against tissue-specific differences between the nerve and hDRG. Using a combination of multi-omic analyses andin vitrofunctional support, we then examined sex-differences, highlighting TNFα signalling as a relevant sexually dimorphic pathway in males. These results support a functional sexually dimorphism in the periphery, which is of particular importance to sensory– and pain-related clinical translation.
Rates of evolution differ between cell types identified by single-cell RNAseq in threespine stickleback
Authors: Rodgers Maria L. , Subramanian Swapna , Fuess Lauren E. , He Wan , Scarpino Samuel V. , Roth-Monzón Andrea J. , Jeffries Daniel , Seignon Martine , Milligan-McClellan Kathryn , Carrier Rebecca , Steinel Natalie C. , Bolnick Daniel I. 
Published: December 2024

AbstractRates of evolutionary change vary by gene. While some broad gene categories are highly conserved with little divergence over time, others undergo continuous selection pressure and are highly divergent. Here, we combine single-cell RNA sequencing (scRNAseq) with evolutionary genomics to understand whether certain cell types exhibit faster evolutionary divergence (using their characteristic genes), than other types of cells. Merging scRNAseq with population genomic data, we show that cell types differ in the rate at which their characteristic genes evolve, as measured by allele frequency divergence among many populations (FST) and between species (dN/dS ratios). Neutrophils, B cells, and fibroblasts exhibit elevated FSTat characteristic genes, while eosinophils in the intestine and thrombocytes in the head kidney exhibit lower FSTthan the average for 1000 random genes. Gene network centrality also differed between immune- and non-immune-associated genes, and closeness centrality was positively related to gene FST. These results highlight the value of merging single cell RNA sequencing technology with evolutionary population genomic data, and reveal that genes which define immune cell types exhibit especially rapid evolution.
DDI-GPT: Explainable Prediction of Drug-Drug Interactions using Large Language Models enhanced with Knowledge Graphs
Authors: Xu Chengqi , Bulusu Krishna C. , Pan Heng , Elemento Olivier 
Published: December 2024

AbstractIdentifying potential drug-drug interactions (DDIs) before clinical use is essential for patient safety yet remains a significant challenge in drug development. We presented DDI-GPT, a deep learning framework that predicts DDIs by combining knowledge graphs (KGs) and pre-trained large language models (LLMs), enabling early detection of potential drug interactions. We demonstrated that DDI-GPT outperforms current state-of-the-art methods by capturing contextual dependencies between biomedical entities to infer potential DDIs. Through feature attribution methods, we show that our explainable deep learning (DL) models enhance the quality of explanations on the pathways and interactome networks. Using TwoSIDES as our benchmark dataset, DDI-GPT achieved the best performance of 0.964 in AUROC compared with existing DL methods. We also applied DDI-GPT to perform zero-shot prediction on 9,480 DDI records, encompassing 442 distinct drugs from the FDA Adverse Event Reporting System. DDI-GPT can attain a high accuracy of in 0.84 AUROC, with an improvement of 14% compared to the best previously published method. We explored model interpretations on predicted DDIs involving Bruton’s tyrosine kinase (BTK) inhibitors and uncovered CYP3A-enriched signals underlying the contaminant use of BTK inhibitors with other drugs leading to toxicity. Altogether, DDI-GPT, implemented as both a web server platform and a software package, identifies DDI events and offers a deep learning tool for drug safety use with expandable features.
Universal Single Copy Knock-In System inCaenorhabditis elegans: One Plasmid to Target All Chromosomes
Authors: Dinneen Erica , Silva-García Carlos G. 
Published: December 2024

ABSTRACTSuccessful transgenesis in model organisms has dramatically helped us understand gene function, regulation, genetic networks, and potential applications. Here, we introduce the universal single-copy knock-in system (Universal SKI System or U-SKI), designed for inserting any transgene by CRISPR/Cas9 in theCaenorhabditis elegansgenome. The Universal SKI System takes advantage of a plasmid (pSKI), which can also be used for extrachromosomal arrays, to facilitate the insertion of a transgene at specific safe harbor loci on each autosomal chromosome. The pSKI plasmid contains multiple restriction sites for easy cloning and serves as a CRISPR/Cas9-based insertion repair template because it has two synthetic and long homology arms that recombine with the SKI cassettes. This system also uses a single crRNA guide, which acts as a Co-CRISPR enrichment marker. Overall, the Universal SKI System is highly flexible; with the same Universal SKI cassette on each autosome, researchers can select the insertion site and streamline tracking while reducing the complexity of expressing single-copy transgenes inC. elegans.
Cobalt induces the set-up of new structural networks in river biofilms: Impairment of autotrophic-heterotrophic coupling
Authors: Gourgues Sarah , Goñi-Urriza Marisol , Baldoni-Andrey Patrick , Bagger Gurieff Nicholas , Gelber Clémentine , Le Faucheur Séverine 
Published: December 2024

AbstractBiofilms play a crucial role in biogeochemical cycles, making them essential to the functionality and stability of aquatic ecosystems. Their functioning is mainly driven by interactions between microorganisms that ensure the cycling of major elements. Evaluating the impact of stressors, such as metals, on these interactions is challenging. This study examined the effects of cobalt (Co) on the microeukaryotic community and their relationships with prokaryotes within biofilms grown in the presence of several Co concentrations (background concentrations, 0.1, 0.5, and 1 µM) for 28 days and 35 days after the end of Co injection. A previous work has suggested thatCyanobacteriawere highly sensitive to Co leading to a reduction of the photosynthetic potential of the biofilm. In this study, the major primary producers, namelyBacillariophyceae,were also found to be sensitive to Co. The direct consequence of this sensitivity was an impairment of the autotroph-heterotroph coupling and the dominance of prokaryotic taxa in microbe-microbe interactions. The biofilms co-occurrence networks were then smaller, less connected but more centralized at 1 µM Co. Keystones, that were half affiliated with microalgae in the absence of Co, were mostly prokaryotes. As such, prokaryotes were found to control resource production and element cycling in Co-stressed biofilms. These changes in co-occurrence network organization and microbial community composition demonstrated a cascade of effects related to contamination in rivers. Our results further highlighted the strategy biofilms adopt to counteract the impairment of autotroph-heterotroph coupling, and to maintain their functions and ecosystemic roles in contaminated environments.
Identification of Gene Targets for the Sprouting Inhibitor CIPC
Authors: Grand Thomas M , Pitman James K , Williams Alexander L , Smith Lisa M , Fleming Andrew J 
Published: December 2024

AbstractSprout suppressants are widely used in industry to ensure year-round availability of potato tubers, significantly decreasing wastage by repressing premature growth of buds on the tuber surface during storage. Despite its ban from 2020 in the EU, isopropyl N-(3- chlorophenyl) carbamate (also known as chlorpropham or CIPC) remains the most widely used suppressant world-wide. However, the mechanism of action of CIPC remains obscure. Here we report on a combined targeted transcriptomic and genetic approach to identify components in the tuber bud cell-division machinery that might be involved in CIPC’s mode of action. This involved RNAseq analysis of dissected, staged tuber buds during in vitro sprouting with and without CIPC to identify lead genes, followed by the development and application of an Arabidopsis root assay to assess cell division response to CIPC in selected mutants. The ease of use of this model plant, coupled with its immense genetic resources, allowed us to test the functionality of lead genes encoding cell-division associated proteins in the modulation of plant growth response to CIPC. This approach led to the identification of a component of the augmin complex (a core player in mitosis) as a potential target for CIPC.
Transcriptomic Analysis Reveals MSTN Mutations and Mechanisms of Muscle Hypertrophy in a New Guinea Pig Breed
Authors: Carmen Sheyla , Chauca Lilia , Yalta Claudia , Alvarado Enrique , Mellisho Edwin 
Published: December 2024

ABSTRACTThe guinea pig (Cavia porcellus), a species native to Peru, is valued for its meat production, where muscle development is essential for productive efficiency. The new Kuri breed, obtained through selective breeding and genetic selection, has shown a phenotype with more developed musculature compared to native guinea pigs. In this study, we conducted a comparative transcriptomic analysis between Native and Kuri breed guinea pig, complemented by histological analysis of the semitendinosus muscle to investigate the underlying mechanisms responsible for the differences in muscle morphology. Histological analysis revealed a significant increase in muscle fiber area in the Kuri breed compared to the native guinea pigs. At the molecular level, key mutations were identified in theMSTNgene, including variants in the 3’ UTR region and a frameshift mutation, which alter the gene’s inhibitory function on muscle growth. Additionally, differences were observed in the expression of pathways related to muscle degradation, energy metabolism, and angiogenesis, which explain the greater muscle hypertrophy in the Kuri breed. These findings provide a first understanding of the genetic mechanisms responsible for muscle hypertrophy in the Kuri breed and suggest candidate genes for improving meat quality through molecular genetic breeding programs in guinea pigs.AUTHOR SUMMARYThe guinea pig in Peru is valued for its meat production. The new Kuri breed, obtained through selective breeding and genetic selection has shown a phenotype with more developed musculature compared to other breeders. In our study, comparative transcriptomic analysis between Native and Kuri breed guinea pig, complemented by histological analysis of the semitendinosus muscle to investigate the underlying mechanisms responsible for the differences in muscle morphology. Histological analysis showed significant increase in muscle fiber area in the Kuri breed compared to the native. Furthermore, it is the first time that we identify in guinea pig, key mutations in the MSTN gene, which alter the gene’s inhibitory function on muscle growth. The impact of this finding will allow us to plan genetic improvement strategies in this species that promote muscle hypertrophy, paving the way for future research and its potential impact on guinea pig production.