bluuebunny/crossref_metadata_2025_split huggingface dataset:
Binning meets taxonomy: TaxVAMB improves metagenome binning using bi-modal variational autoencoder
Authors: Kutuzova Svetlana , Piera Pau , Nor Nielsen Knud , Olsen Nikoline S. , Riber Leise , Gobbi Alex , Forero-Junco Laura Milena , Dougherty Peter Erdmann , Westergaard Jesper Cairo , Christensen Svend , Hansen Lars Hestbjerg , Nielsen Mads , Nissen Jakob Nybo , Rasmussen Simon 
Published: October 2024

AbstractA common procedure for studying the microbiome is binning the sequenced contigs into metagenome-assembled genomes. Currently, unsupervised and self-supervised deep learning based methods using co-abundance and sequence based motifs such as tetranucleotide frequencies are state-of-the-art for metagenome binning. Taxonomic labels derived from alignment based classification have not been widely used. Here, we propose TaxVAMB, a metagenome binning tool based on semi-supervised bi-modal variational autoencoders, combining tetranucleotide frequencies and contig co-abundances with contig annotations returned by any taxonomic classifier on any taxonomic rank. TaxVAMB outperforms all other binners on CAMI2 human microbiome datasets, returning on average 40% more near-complete assemblies than the next best binner. On real long-read datasets TaxVAMB recovers on average 13% more near-complete bins and 14% more species. When used in a single-sample setup, TaxVAMB on average returns 83% more high quality bins than VAMB. TaxVAMB bins incomplete genomes drastically better than any other tool, returning 255% more high quality bins of incomplete genomes than the next best binner. Our method has immediate research and industrial applications, as well as methodological novelty which can be translated to other biological problems with semi-supervised multimodal datasets.
Agroforestry adoption and its influence on soil quality under smallholder maize production systems in western Kenya
Authors: Nyuma H.T , Njoroge R , Otinga A.N 
Published: October 2024

ABSTRACTAgroforestry, a sustainable land use practice was-introduced in western Kenya in the early 1990’s as a soil fertility replenishment strategy alongside other multiple benefits. Since then, effect of the practice on soil quality is seldom evidenced. Therefore, a study was conducted in the region to assess the effects of agroforestry adoption on soil quality under small holder maize production systems. A total of 120 soil samples were collected from two land use practices: agroforestry adoption (90) and non-agroforestry adoption (30) at 0-30 cm depth from two locations (Busia and Kakamega counties). On average, adoption of agroforestry significantly improved soil physicochemical properties compared to non-adoption of agroforestry. Bulk density (BD) reduced by 21% (from 1.4 to1.1g cm−3)while SOC increased by 75% (0.8-1.4%), P by 80% (3.0-5.4 mg kg−1), exchangeable K+by 256% (0.3-8.0 Cmolc kg−1), Ca2+by 100% (1.0-2.0 Cmolc kg−1), S by 50%(0.2-0.3 mg kg−1), and Cu by 18% (2.8-3.3 mg kg−1).In reference to the soil environmental requirement for maize production, agroforestry adoption significantly increased K and Cu above the critical thresholds of 0.4 Cmolc kg−1and 1.0 mg kg−1, respectively regardless of the study location or adoption practice. In addition, different agroforestry tree species had variable effect on soil properties. Sesbania and leucaena significantly influenced soil BD, clay, pH, Similarly, soil available P (4.3.-7.0 mg kg−1), exchangeable K+(0.4-0.7 cmolc kg−1), Mg (0.1-0.2 cmolc kg−1), and Mn (13.5 – 25.2 mg kg−1) above non-agroforestry adoption at both locations, while calliandra significantly increased SOC in Kakamega only.
DNA nanodevice for analysis of force-activated protein extension and interactions
Authors: Zhou Kun , Chung Minhwan , Cheng Jing , Powell John T. , Yan Qi , Liu Jun , Xiong Yong , Schwartz Martin A. , Lin Chenxiang 
Published: October 2024

AbstractForce-induced changes in protein structure and function mediate cellular responses to mechanical stresses. Existing methods to study protein conformation under mechanical force are incompatible with biochemical and structural analysis. Taking advantage of DNA nanotechnology, including the well-defined geometry of DNA origami and programmable mechanics of DNA hairpins, we built a nanodevice to apply controlled forces to proteins. This device was used to study the R1-R2 segment of the talin1 rod domain as a model protein, which comprises two alpha-helical bundles that reversibly unfold under tension to expose binding sites for the cytoskeletal protein vinculin. Electron microscopy confirmed tension-dependent protein extension while biochemical analysis demonstrated enhanced vinculin binding under tension. The device could also be used in pull down assays with cell lysates, which identified filamins as novel tension-dependent talin binders. The DNA nanodevice is thus a valuable addition to the molecular toolbox for studying mechanosensitive proteins.
Decoding the Functional Interactome of Non-Model Organisms with PHILHARMONIC
Authors: Sledzieski Samuel , Versavel Charlotte , Singh Rohit , Ocitti Faith , Devkota Kapil , Kumar Lokender , Shpilker Polina , Roger Liza , Yang Jinkyu , Lewinski Nastassja , Putnam Hollie , Berger Bonnie , Klein-Seetharaman Judith , Cowen Lenore 
Published: October 2024

AbstractProtein-protein interaction (PPI) networks are a fundamental resource for modeling cellular and molecular function, and a large and sophisticated toolbox has been developed to leverage their structure and topological organization to predict the functional roles of under-studied genes, proteins, and pathways. However, the overwhelming majority of experimentally-determined interactions from which such networks are constructed come from a small number of well-studied model organisms. Indeed, most species lack even a single experimentally-determined interaction in these databases, much less a network to enable the analysis of cellular function, and methods for computational PPI prediction are too noisy to apply directly. We introduce PHILHARMONIC, a novel computational approach that couples deep learningde novonetwork inference with robust unsupervised spectral clustering algorithms to uncover functional relationships and high-level organization in non-model organisms. Our clustering approach allows us to de-noise the predicted network, producing highly informative functional modules. We also develop a novel algorithm called ReCIPE, which aims to reconnect disconnected clusters, increasing functional enrichment and biological interpretability. We perform remote homology-based functional annotation by leveraging hmmscan and GODomainMiner to assign initial functions to proteins at large evolutionary distances. Our clusters enable us to newly assign functions to uncharacterized proteins through “function by association.” We demonstrate the ability of PHILHARMONIC to recover clusters with significant functional coherence in the reef-building coralP. damicornis, its algal symbiontC. goreaui, and the well-annotated fruit flyD. melanogaster. We perform a deeper analysis of theP. damicornisnetwork, where we show that PHILHARMONIC clusters correlate strongly with gene co-expression and investigate several clusters that participate in temperature regulation in the coral, including the first putative functional annotation of several previously uncharacterized proteins. Easy to run end-to-end and requiring only a sequenced proteome, PHILHARMONIC is an engine for biological hypothesis generation and discovery in non-model organisms.PHILHARMONIC is available athttps://github.com/samsledje/philharmonic
Generation of T cells with reduced off-target cross-reactivities by engineering co-signalling receptors
Authors: Cabezas-Caballero Jose , Huhn Anna , Kutuzov Mikhail A. , Andre Violaine , Shomuradova Alina , van der Merwe P. Anton , Dushek Omer 
Published: October 2024

AbstractAdoptive T cell therapy using T cells engineered with novel T cell receptors (TCRs) targeting tumor-specific peptides is a promising immunotherapy. However, these TCR-T cells can cross-react with off-target peptides, leading to severe autoimmune toxicities. Current efforts focus on identifying TCRs with reduced cross-reactivity. Here, we show that T cell cross-reactivity can be controlled by the co-signalling molecules CD5, CD8, and CD4, without modifying the TCR. We find the largest reduction in cytotoxic T cell cross-reactivity by knocking out CD8 and expressing CD4. Cytotoxic T cells engineered with a CD8-to-CD4 co-receptor switch show reduced cross-reactivity to random and positional scanning peptide libraries, as well as to self-peptides, while maintaining their on-target potency. Therefore, co-receptor switching generates super selective T cells that reduce the risk of lethal off-target cross-reactivity, and offers a universal method to enhance the safety of T cell immunotherapies for any TCR.Graphical abstractOne sentence summarySwitching the CD8 for the CD4 co-receptor in cytotoxic T cells reduces the functional cross-reactivity of T cells without modifying the TCR.
Phosphorylation of HP1/Swi6 relieves competition with Suv39/Clr4 on nucleosomes and enables H3K9 trimethyl spreading
Authors: Kennedy Dana R , Lemiere Joel , Tan Catherine , Simental Eric , Braxton Julian , Maxwell Robert A , Amine Ahmed AA , Al-Sady Bassem 
Published: October 2024

ABSTRACTHeterochromatin formation in Schizosaccharomyces pombe requires the spreading of histone 3 (H3) Lysine 9 (K9) methylation (me) from nucleation centers by the H3K9 methylase, Suv39/Clr4, and the reader protein, HP1/Swi6. To accomplish this, Suv39/Clr4 and HP1/Swi6 have to associate with nucleosomes both nonspecifically, binding DNA and octamer surfaces and specifically, via recognition of methylated H3K9 by their respective chromodomains. However, how both proteins avoid competition for the same nucleosomes in this process is unclear. Here, we show that phosphorylation tunes the nucleosome affinity of HP1/Swi6 such that it preferentially partitions onto Suv39/Clr4’s trimethyl product rather than its unmethylated substrates. Preferential partitioning enables efficient conversion from di-to trimethylation on nucleosomes in vitro and H3K9me3 spreading in vivo. Together, our data suggests that phosphorylation of HP1/Swi6 creates a regime that relieves competition with the “read-write” mechanism of Suv39/Clr4 for productive heterochromatin spreading.
5hmC enhances PARP trapping and restores PARP inhibitor sensitivity in chemoresistant BRCA1/2-deficient cells
Authors: Kharat Suhas S. , Mishra Arun P. , Sengodan Satheesh K. , Dierman Dillon , Fox Stephen D. , Sharan Shyam K. 
Published: October 2024

AbstractMutations inBRCA1andBRCA2genes are the leading cause of hereditary breast and ovarian cancer.BRCA1/2-mutant cells are defective in repairing damaged DNA by homologous recombination and are characterized by hypersensitivity to PARP inhibitors. PARP inhibitors can trap PARP proteins on the chromatin, a mechanism that can contribute to the death of BRCA1/2-deficient cells. The FDA has approved multiple PARP inhibitors for the treatment of metastatic breast and ovarian cancers, but despite the success of PARP inhibitors in treatingBRCA1/2-mutant cancers, drug resistance is a major challenge. Here, we report that 5hmC enhances PARP1 trapping on the chromatin in olaparib-treated cells. Elevated PARP trapping generates replication gaps, leading to the restoration of PARP inhibitor sensitivity in chemoresistant BRCA1/2-deficient cells. Our findings suggest that combining 5hmC with olaparib can restore the sensitivity of chemoresistant BRCA1/2-deficient cells.
Sensitivity to photoperiod is a complex trait inCamelina sativa
Authors: Ramirez-Corona Bryan A , Seagren Erin , Sherman Carissa , Imaizumi Takato , Queitsch Christine , Cuperus Josh 
Published: October 2024

SummaryDay neutrality, or insensitivity to photoperiod (day length), is an important domestication trait in many crop species. Although the oilseed cropCamelina sativahas been cultivated since the Neolithic era, day-neutral accessions have yet to be described. We sought to leverage genetic diversity in existing germplasms to identifyC. sativaaccessions with low photoperiod sensitivity for future engineering of this trait. We quantified variation in the photoperiod response across 161 accessions ofC. sativaby measuring hypocotyl length of four-day-old seedlings grown in long-day and short-day conditions, finding wide variation in photoperiod response. Similarly, soil-grown adult plants from selected accessions showed variation in photoperiod response in several traits; however, photoperiod responses in seedling and adult traits were not correlated, suggesting complex mechanistic underpinnings. Although RNA-seq experiments of the reference accession Licalla identified several differentially regulatedArabidopsissyntelogs involved in photoperiod response, includingCOL2, FT, LHYandWOX4, expression of these genes in the accessions did not correlate with differences in their photoperiod sensitivity. Taken together, we show that all tested accessions show some degree of photoperiod response, and that this trait is likely complex, involving several and separable seedling and adult traits.Significance StatementDay neutrality (photoperiod insensitivity) is a common trait in domesticated crops; however, the ancient oilseed cropCamelina sativahas remained photoperiod-sensitive, which likely limits seed yields. Here, we show that photoperiod sensitivity is conserved across manyC. sativacultivars, albeit to different degrees, and we establish that photoperiod sensitivity is a complex trait, which will require genetic engineering to achieve day neutrality.
Deep Learning Prediction of Parkinson’s Disease using Remotely Collected Structured Mouse Trace Data
Authors: Shahriar Zawad Md Rahat , Tumpa Zerin Nasrin , Sollis Lydia , Parab Shubham , Washington Peter 
Published: October 2024

AbstractParkinson’s Disease (PD) is the second most common neurodegenerative disorder globally, and current screening methods often rely on subjective evaluations. We developed deep learning-based classification models using mouse trace data collected via a web application. 315 participants (73 PD, 179 non-PD, 63 suspected PD) completed three hand movement tasks: tracing a straight line, spiral, and sinewave. We developed three types of models: (1) engineered features models, (2) computer vision models, and (3) multimodal models. Feature importance was evaluated using Gradient Shapley Additive Explanations (GradShap). The multimodal Visual transformer (ViT) model achieved the highest performance, with F1 scores of 0.8413 ± 0.0336 (PD vs. non-PD), 0.8520 ± 0.0014 (suspected PD vs. non-PD), and 0.7034 ± 0.0017 (PD vs. suspected PD). Image data proved most influential in predicting PD outcomes. These findings suggested that models trained on confirmed PD diagnoses hold significant promise for early-stage PD screening at the population level.
Phage-plasmid borne methionine tRNA ligase mediates epidemiologically relevant antimicrobial persistence
Authors: Tam Yi Ling , De Silva P. Malaka , Barker Clare R. , Li Ruizhe , Batisti Biffignandi Gherard , Santos Leanne , Chong Charlotte E. , Mason Lewis C. E. , Nair Satheesh , Ribeca Paolo , Bayliss Sion C. , Jenkins Claire , Bakshi Somenath , Hall James P.J. , Cowley Lauren , Baker Kate S. 
Published: October 2024

AbstractAntimicrobial resistance (AMR) is a global public health crisis with few options for control. As such early identification of emerging bacterial strains capable of rapidly evolving AMR is key. Although antimicrobial tolerance and persistence are precursor phenotypes for AMR, little evidence exists to support their importance in real-world settings. Here we used bacterial genome wide association on national genomic surveillance data of the diarrhoeal pathogenShigella sonnei(n=3745) to agnostically identify common genetic signatures among lineages convergently evolving toward AMR (n=15). This revealed an association of an AMR trajectory with a multi- and highly variable second copy ofmetG, borne by a phage-plasmid we called pWPMR2. Further analyses revealed that pWPMR2 was present across clinically relevant enteric pathogens globally, including past and contemporary outbreaks, and that the additional-metGmechanism was present across multiple bacterial phyla. Functional microbiology, experimental evolution, and single-cell physiology studies confirmed that the expression of auxiliarymetG, particularly the mutated version on pWPMR2, created a sub population of persister cells predisposed to survival in, and evolving resistance against, third generation cephalosporins. Thus, we demonstrate a novel mechanism of auxiliarymetGcarriage that predisposes bacteria to AMR with real world impacts. Furthermore, our approach is a timely example of using genomic epidemiology to rapidly guide functional microbiology studies in the era of routine genomic surveillance, and also highlights several deficiencies in current AMR surveillance practices.
A survey on the nationwide prevalence of asbestos-related lung cancer in Japan
Authors: Niino Mariko , Tomizuka Taro , Nishina Yuka , Ichinose Yuichi , Gonoi Wataru , Higashi Takahiro 
Published: October 2024

AbstractBACKGROUNDAn accurate estimate of the nationwide prevalence of asbestos-related lung cancer (ARLC) is necessary to adequately operate a compensation subsidy program for patients with ARLC. Our study aimed to estimate the proportion of patients with ARLC among patients with primary lung cancer, and describe the characteristics and distribution of ARLC.METHODSAll facilities that treated patients diagnosed with lung cancer in 2016 were requested to submit computed tomography images of 10 patients randomly selected from the national databases of hospital-based cancer registries. ARLC was defined as pleural plaques (PPs) extending over one-quarter of the inner lateral chest wall or existing PPs accompanied by obvious lung fibrosis. We estimated the proportion and distribution of ARLC among primary lung cancer cases and compared the characteristics of ARLC with those of primary lung cancer.RESULTSOf 772 facilities that treated at least one patient with lung cancer, 370 provided 3,565 sets of CT images. Of these, 216 (6.1%) had PPs, and 86 (2.4%) met the compensation criteria. After sample weighting, 2.0% of all primary lung cancers were classified as ARLC in Japan. A higher percentage of patients with ARLC were male (94.2% vs. 68.6%;P< .01) and had more advanced-stage disease (stage III: 22.1% vs. 16.0%; stage IV: 44.2% vs. 39.8%;P=.05) than other primary lung cancers. A majority (53.5%) of patients with ARLC were diagnosed at designated cancer hospitals. The proportion of squamous cell carcinoma was higher in ARLC than in those with primary lung cancer (25.6% vs. 18.6%;P< .01).CONCLUSIONThe estimated number of patients with ARLC was larger than expected from the number of applicants in the compensation system for asbestos-related health damages (AHDRS). Consequently, countermeasures are required to accurately identify eligible compensation recipients.HighlightThe estimated proportion of patients with ARLC among patients with lung cancer was 2%.The proportion of squamous cell carcinoma was higher in ARLC than in primary lung cancer.A higher number of ARLC cases than expected from the official reports of AHDRS compensation recipients in Japan was found. More accurate AHDR reports are needed
Motif-induced Subgraph Generative Learning for Explainable Neurological Disorder Detection
Authors: Liu Mujie , Dong Qichao , Wang Chenze , Cheng Xinrui , Febrinanto Falih Gozi , Hoshyar Azadeh Noori , Xia Feng 
Published: October 2024

AbstractThe wide variation in symptoms of neurological disorders among patients necessitates uncovering individual pathologies for accurate clinical diagnosis and treatment. Current methods attempt to generalize specific biomarkers to explain individual pathology, but they often lack analysis of the underlying pathogenic mechanisms, leading to biased biomarkers and unreliable diagnoses. To address this issue, we propose a motif-induced subgraph generative learning model (MSGL), which provides multi-tiered biomarkers and facilitates explainable diagnoses of neurological disorders. MSGL uncovers underlying pathogenic mechanisms by exploring representative connectivity patterns within brain net-works, offering motif-level biomarkers to tackle the challenge of clinical heterogeneity. Furthermore, it utilizes motif-induced information to generate enhanced brain network subgraphs as personalized biomarkers for identifying individual pathology. Experimental results demonstrate that MSGL outperforms baseline models. The identified biomarkers align with recent neuroscientific findings, enhancing their clinical applicability.
Proximity Interactome analyses unveil novel regulators of IRE1α canonical signaling
Authors: Le Goupil Simon , Philippe Céline , Laprade Hadrien , Lode Mathéo , Boniface Rachel , Pelizzari-Raymundo Diana , Dejgaard Kurt , Jansen Gregor , Limia Celia , Hetz Claudio , Mahdizadeh S. Jalil , Negroni Luc , Aubry Marc , Ricci Jean-Ehrland , Eriksson Leif A. , Chevet Eric 
Published: October 2024

AbstractThe unfolded protein response (UPR) is a key adaptive pathway that controls endoplasmic reticulum (ER) homeostasis. The UPR is transduced by three ER-resident sensors of ER homeostasis disruption in the lumen of this compartment. They trigger select downstream signaling pathways in the cytosol and nucleus. Among them, IRE1α (referred to as IRE1 hereafter), a type I transmembrane protein, senses accumulation of improperly folded proteins in the ER lumen and transduces signals through both kinase and endoribonuclease (RNase) activities in the cytosol. IRE1 catalyzesXBP1mRNA unconventional splicing and RNA degradation (Regulated IRE1 Dependent Decay, termed RIDD). Recent studies have reported that IRE1-dependent protein-protein interactions (PPi) drive additional non-canonical IRE1 functions. Herein, we define the IRE1 signalosome as a list of IRE1 binding partners (direct or not) which alter IRE1 signaling towards XBP1 mRNA splicing and RIDD. Here we determined the IRE1in situinteractome using BioID, putatively connecting IRE1 to previously unrecognized cellular functions. In addition, we link the binding of several IRE1 partners to the regulation of its RNase. Furthermore, we identify HNRNPL as an IRE1-interacting partner, previously unrecognized, which stabilizes IRE1 under basal conditions by counteracting ERAD-mediated degradation. Overall, the characterization of the IRE1 signalosome not only reveals the multi-faceted control of IRE1 RNase activity and stability by its interacting partners and allow us to discuss putative additional IRE1 regulators and cellular functions based on the nature of its interactome and its localization.