bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detecting known neoepitopes, gene fusions, transposable elements, and circular RNAs in cell-free RNA
Authors: Mahajan Mayank , Hemberg Martin 
Published: June 2024

ABSTRACTCancer is the second leading cause of death worldwide, and although there have been advances in treatments, including immunotherapies, these often require biopsies which can be costly and invasive to obtain. Due to lack of pre-emptive cancer detection methods, many cases of cancer are detected at a late stage when the definitive symptoms appear. Plasma samples are relatively easy to obtain, and they can be used to monitor the molecular signatures of ongoing processes in the body. Profiling cell-free DNA is a popular method for monitoring cancer, but only a few studies have explored the use of cell-free RNA (cfRNA), which shows the recent footprint of systemic transcription. Here we developed FastNeo, a computational method for detecting known neoepitopes in human cfRNA. We show that neoepitopes and other biomarkers detected in cfRNA can discern Hepatocellular carcinoma (HCC) patients from the healthy patients with a sensitivity of 0.84 and a specificity of 0.79. For colorectal cancer we achieve a sensitivity of 0.87 and a specificity of 0.8. An important advantage of our cfRNA based approach is that it also reports putative neoepitopes which are important for therapeutic purposes.
The genetic basis of the black pupae phenotype in tephritid fruit flies
Authors: Paulo Daniel F. , Nguyen Thu N.M. , Ward Chris M. , Corpuz Renee L. , Kauwe Angela N. , Rendon Pedro , Ruano Rocio E.Y. , Cardoso Amanda A.S. , Gouvi Georgia , Fung Elisabeth , Crisp Peter , Okada Anzu , Choo Amanda , Stauffer Christian , Bourtzis Kostas , Sim Sheina B. , Baxter Simon W. , Geib Scott M. 
Published: June 2024

AbstractThe remarkable diversity of insect pigmentation offers a captivating avenue for exploring evolution and genetics. In tephritid fruit flies, decoding the molecular pathways underlying pigmentation traits also plays a central role in applied entomology. Mutant phenotypes like the black pupae (bp) have long been used as a component of genetic sexing strains, allowing male-only release in tephritid sterile insect technique applications. However, the genetic basis of bp remains largely unknown. Here, we present independent evidence from classical and modern genetics showing that the bp phenotype in the GUA10 strain of the Mexican fruit fly,Anastrepha ludens, is caused by a large deletion at theebonylocus resulting in the removal of the entire protein-coding region of the gene. Targeted knockout ofebonyinduced analogous bp phenotypes across six tephritid species spanning over 50 million years of divergent evolution. This functionally validated our findings and allowed for a deeper investigation into the role of Ebony in pigmentation and development in these species. Our study offers fundamental knowledge for developing new sexing strains based on the bp marker and for future evolutionary developmental biology studies in tephritid fruit flies.
Exon Nomenclature and Classification of Transcripts (ENACT): Systematic framework to annotate exon attributes
Authors: Verma Paras , Thakur Deeksha , Pandit Shashi Bhushan 
Published: June 2024

AbstractMotivationIsoform diversity is known to enhance a gene’s functional repertoire. Despite studies on transcriptome diversifying processes (Alternate splicing/transcription), their extent and correlated impact on proteome diversity remains rudimentarily understood.ResultsThe current study presents an innovative framework, “Exon Nomenclature and Annotation of Transcripts,” that centralizes exonic loci while integrating protein sequenceper entitywith tracking and assessing splice site variability. The resulting annotation from framework enables exon features to be tractable, facilitating a systematic analysis of isoform diversity. Our findings and case studies unveil systemic exon inclusion’s roles in regulating diversity in CDS region.Availability and implementationAll data generated during this study are publicly available atwww.iscbglab.in/enactdb/. Associated algorithmic procedures have been described in the methods section.Supplementary informationPDF file enclosing supplementary data attached.
Differences in systemic immune parameters in individuals with lung cancer according to race
Authors: von Itzstein Mitchell S. , Liu Jialiang , Mu-Mosley Hong , Fattah Farjana , Park Jason Y. , SoRelle Jeffrey A. , Farrar J. David , Gwin Mary E. , Hsiehchen David , Gloria-McCutchen Yvonne , Wakeland Edward K. , Cole Suzanne , Bhalla Sheena , Kainthla Radhika , Puzanov Igor , Switzer Benjamin , Daniels Gregory A. , Zakharia Yousef , Shaheen Montaser , Zhang Jianjun , Xie Yang , Gerber David E. 
Published: June 2024

AbstractIntroductionRacial and ethnic disparities in the presentation and outcomes of lung cancer are widely known. To evaluate potential factors contributing to these observations, we measured systemic immune parameters in Black and White patients with lung cancer.MethodsPatients scheduled to receive cancer immunotherapy were enrolled in a multi-institutional prospective biospecimen collection registry. Clinical and demographic information were obtained from electronic medical records. Pre-treatment peripheral blood samples were collected and analyzed for cytokines using a multiplex panel and for immune cell populations using mass cytometry. Differences between Black and White patients were determined and corrected for multiple comparisons.ResultsA total of 187 patients with non-small cell lung cancer (Black, 19; White, 168) were included in the analysis. There were no significant differences in baseline characteristics between Black and White patients. Compared to White patients, Black patients had significantly lower levels of CCL23 and CCL27, and significantly higher levels of CCL8, CXCL1, CCL26, CCL25, CCL1, IL-1 b, CXCL16, and IFN-γ (allP<0.05, FDR<0.1). Black patients also exhibited greater populations of non-classical CD16+ monocytes, NKT-like cells, CD4+ cells, CD38+ monocytes, and CD57+ gamma delta T cells (allP<0.05).ConclusionsBlack and White patients with lung cancer exhibit several differences in immune parameters, with Black patients exhibiting greater levels of numerous pro-inflammatory cytokines and cell populations. The etiology and clinical significance of these differences warrant further evaluation.
Diminished Immune Cell Adhesion in Hypoimmune ICAM-1 Knockout Pluripotent Stem Cells
Authors: Saha Sayandeep , Haynes W. John , Del Rio Natalia M. , Young Elizabeth E. , Zhang Jue , Seo Jiwon , Huang Liupei , Holm Alexis M. , Blashka Wesley , Murphy Lydia , Scholz Merrick J. , Henrichs Abigale , Suresh Babu Jayalaxmi , Steill John , Stewart Ron , Kamp Timothy J. , Brown Matthew E. 
Published: June 2024

AbstractHypoimmune gene edited human pluripotent stem cells (hPSCs) are a promising platform for developing reparative cellular therapies that evade immune rejection. Existing first-generation hypoimmune strategies have used CRISPR/Cas9 editing to modulate genes associated with adaptive (e.g., T cell) immune responses, but have largely not addressed the innate immune cells (e.g., monocytes, neutrophils) that mediate inflammation and rejection processes occurring early after graft transplantation. We identified the adhesion molecule ICAM-1 as a novel hypoimmune target that plays multiple critical roles in both adaptive and innate immune responses post-transplantation. In a series of studies, we found that ICAM-1 blocking or knock-out (KO) in hPSC-derived cardiovascular therapies imparted significantly diminished binding of multiple immune cell types. ICAM-1 KO resulted in diminished T cell proliferation responsesin vitroand in longerin vivoretention/protection of KO grafts following immune cell encounter in NeoThy humanized mice. The ICAM-1 KO edit was also introduced into existing first-generation hypoimmune hPSCs and prevented immune cell binding, thereby enhancing the overall hypoimmune capacity of the cells. This novel hypoimmune editing strategy has the potential to improve the long-term efficacy and safety profiles of regenerative therapies for cardiovascular pathologies and a number of other diseases.HighlightsAntibody blocking of ICAM-1 on human pluripotent stem cell-derived cells inhibits immune cell adhesionCRISPR/Cas9 knock-out of ICAM-1 ablates surface and secreted ICAM-1 protein and inhibits immune adhesionICAM-1 knock-out results in decreased T cell proliferative responses to human pluripotent stem cell-derived graftsin vitro, and resistance to immune-mediated graft lossin vivoAddition of ICAM-1 knock-out to first generation MHC knock-out human pluripotent stem cells confers protection against immune adhesionGraphical AbstractICAM-1 Knock-out in Transendothelial Migration and at the Immune Synapse.Abbreviations: PSC-EC – pluripotent stem cell-derived endothelial cells; KO – knock-out; dSMAC – distal supramolecular activation complex; pSMAC – peripheral supramolecular activation complex; cSMAC – central supramolecular activation complex.
Adenine nucleotide translocase 2 silencing promotes metabolic adaptations and anoikis in P19 embryonal carcinoma stem cells
Authors: Oliveira Gabriela L. , Mota Sandra I. , Oliveira Paulo J. , Marques Ricardo 
Published: June 2024

AbstractCancer stem cells (CSCs) are amongst the group of cells constituting tumors, being characterized by their strong self-renewal and survival properties. Cancer cells, CSCs included, are thought to rely mostly on glycolysis, even in the presence of oxygen, which confers them adaptative advantages. Adenine nucleotide translocator 2 (ANT2), responsible for the exchange of ADP and ATP in the mitochondrial inner membrane, has been correlated with a higher glycolytic metabolism and is known to be overexpressed in cancer cells. Using P19 embryonal carcinoma stem cells (P19SCs) as a CSCs model, we inhibit ANT2 translation by using siRNA. ANT2 protein levels were shown to be overexpressed in P19SC when compared to their differentiated counterparts. Furthermore, we showed here that the OXPHOS machinery and mitochondrial membrane potential are compromised after ANT2 depletion, exhibiting a metabolic adaptation towards a less oxidative phenotype. Interestingly, hexokinase II levels were downregulated, which was also accompanied by decreased cell growth, and decreased ability to form spheroids. Our findings underscore ANT2 as a key regulator of metabolic remodeling and cell survival of CSCs, suggesting its potential as a therapeutic target for controlling CSC-driven tumor progression.HighlightsANT2 silencing promotes cell growth arrest and metabolic remodeling in CSCs.ANT2 depletion modulates HKII protein levels.ANT2 induce anoikis resistance in P19SCs
Accelerating Protein-Protein Interaction screens with reduced AlphaFold-Multimer sampling
Authors: Bellinzona G. , Sassera D. , Bonvin A.M.J.J 
Published: June 2024

AbstractMotivationDiscovering new protein-protein interactions (PPIs) across entire proteomes offers vast potential for understanding novel protein functions and elucidate system properties within or between an organism. While recent advances in computational structural biology, particularly AlphaFold-Multimer, have facilitated this task, scaling for large-scale screenings remains a challenge, requiring significant computational resources.ResultsWe evaluated the impact of reducing the number of models generated by AlphaFold-Multimer from five to one on the method’s ability to distinguish true PPIs from false ones. Our evaluation was conducted on a dataset containing both intra- and inter-species PPIs, which included proteins from bacterial and eukaryotic sources. We demonstrate that reducing the sampling does not compromise the accuracy of the method, offering a 5 time faster, efficient, and environmentally friendly solution for PPI predictions.AvailabilityThe code used in this article is available athttps://github.com/MIDIfactory/AlphaFastPPi. Note that the same can be achieved using the latest version of AlphaPulldown available athttps://github.com/KosinskiLab/AlphaPulldown.
Marginated neutrophils in the lungs effectively compete for nanoparticles targeted to the endothelium, serving as a part of the reticuloendothelial system
Authors: Zamora Marco E. , Essien Eno-Obong , Bhamidipati Kartik , Murthy Aditi , Liu Jing , Kim Hyunjun , Patel Manthan N. , Nong Jia , Wang Zhicheng , Espy Carolann , Chaudhry Fatima N. , Ferguson Laura , Tiwari Sachchidanand , Hood Elizabeth , Marcos-Contreras Oscar A. , Omo-Lamai Serena , Shuvaeva Tea , Arguiri Evguenia , Wu Jichuan , Rauova Lubica , Poncz Mortimer , Basil Maria C. , Cantu Edward , Planer Joseph D. , Spiller Kara , Zepp Jarod , Muzykantov Vladimir , Myerson Jacob , Brenner Jacob S. 
Published: June 2024

AbstractNanomedicine has long pursued the goal of targeted delivery to specific organs and cell types but has not achieved this goal with the vast majority of targets. One rare example of success in this pursuit has been the 25+ years of studies targeting the lung endothelium using nanoparticles conjugated to antibodies against endothelial surface molecules. However, here we show that such “endothelial-targeted” nanocarriers also effectively target the lungs’ numerous marginated neutrophils, which reside in the pulmonary capillaries and patrol for pathogens. We show that marginated neutrophils’ uptake of many of these “endothelial-targeted” nanocarriers is on par with endothelial uptake. This generalizes across diverse nanomaterials and targeting moieties and was even found with physicochemical lung tropism (i.e., without targeting moieties). Further, we observed this inex vivohuman lungs andin vivohealthy mice, with an increase in marginated neutrophil uptake of nanoparticles caused by local or distant inflammation. These findings have implications for nanomedicine development for lung diseases. These data also suggest that marginated neutrophils, especially in the lungs, should be considered a major part of the reticuloendothelial system (RES), with a special role in clearing nanoparticles that adhere to the lumenal surfaces of blood vessels.Graphical Abstract
Multi-objective management of naturally regenerating beech forests – An ecological-economic optimization approach
Authors: Schorn Markus E. , Quaas Martin F. , Schenk Hanna , Wirth Christian , Rüger Nadja 
Published: June 2024

AbstractHow can we meet economic objectives of timber harvesting while maintaining the functioning of diverse forest ecosystems? Existing forest models that address this type of question are often complex, data-intensive, challenging to couple with economic optimization models, or can not easily be generalised for uneven-aged mixed-species forests. Here, we develop an ecological-economic optimization model, which integrates a state-of-the-art demographic forest model with a continuous cover forestry harvesting model to optimise efficient and sustainable timber harvesting. As a proof-of-concept, we apply the model to a beech-dominated forest in the Hainich-Dün region in Thuringia, Germany, with the goal of optimising multiple objectives such as timber yield and the biodiversity value of the forest. The ecological module is the Perfect Plasticity Approximation (PPA) demographic forest model that simulates forest dynamics based on individual tree growth and survival rates in the canopy and understory layers, respectively, as well as recruitment rates. We used repeated forest inventory data from a 28-ha forest plot to quantify these demographic rates and validated the predictions of the ecological module against the structure of old-growth beech forests in Europe. The economic module includes the optimization of net revenues (market revenues net of harvesting cost) from harvesting timber. As an indicator of the biodiversity value of the forest, we use the number of retained habitat trees (>70 cm diameter). The forest model delivered reasonable predictions of structural attributes of unmanaged old-growth beech forests. When net revenues from timber harvest were maximised, trees were logged when they reached 55 cm in diameter. This is similar to current management practices in beech forests. We found a linear trade-off between timber net revenues and biodiversity value with about 2.5% of the maximum benefit of timber harvest being lost with each additionally retained habitat tree. We established a generic ecological-economic modelling framework that reliably represents forest dynamics as well as optimising forest management. To our knowledge, this is the first forest model for central European forests capable of identifying optimal harvesting over the full set of feasible strategies, rather than merely comparing predefined management scenarios. The framework can be extended to mixed-species forests and support forest management for diverse ecosystem services.
Strain identity effects contribute more toPseudomonascommunity functioning than strain interactions
Authors: Kramer Jos , Maréchal Simon , Figueiredo Alexandre R.T. , Kümmerli Rolf 
Published: June 2024

ABSTRACTMicrobial communities can shape key ecological services, but the determinants of their functioning often remain little understood. While traditional research predominantly focuses on effects related to species identity (community composition and species richness), recent work increasingly explores the impact of species interactions on community functioning. Here, we conducted experiments with replicated small communities of fluorescentPseudomonasbacteria to quantify the relative importance of strain identity versus interaction effects on two important functions, community productivity and siderophore production. By combining supernatant and competition assays with an established linear model method, we show that both factors have significant effects on functioning, but identity effects generally outweigh strain interaction effects. These results hold irrespective of whether strains interactions are inferred statistically or approximated experimentally. Our results have implications for microbiome engineering, as the success of approaches aiming to induce beneficial (probiotic) strain interactions will be sensitive to strain identity effects in many communities.
SeqLengthPlot: An easy-to-use Python-based Tool for Visualizing and Retrieving Sequence Lengths from fasta files with a Tunable Splitting Point
Authors: Domínguez-Pérez Dany , Agüero-Chapin Guillermin , Leone Serena , Modica Maria Vittoria 
Published: June 2024

AbstractMotivationAccurate sequence length profiling is essential in bioinformatics, particularly in genomics and proteomics. Existing tools like SeqKit and the Trinity toolkit, among others provide basic sequence statistics but often fall short in offering comprehensive analytics and plotting options. For instance, SeqKit is a very complete and fast tool for sequence analyses, that delivers useful metrics (e.g., number of sequences, average, minimum, maximum length), and can returns the range of sequence shorter or longer (one side, not both at once) on a given lengths. Similarly, Trinity’s utility pearl-based scripts provide detailed contig length distributions (e.g., N50, median, and average lengths) but do not encompass the total number of sequences nor offer graphical representations of data.ResultsGiven that key sequence analysis tasks are distributed among separate tools, we introduce SeqLengthPlot: an easy-to-use Python-based script that fills existing gaps in bioinformatics tools on sequence length profiling, crucial. SeqLengthPlot generates comprehensive statistical summaries, filtering and automatic sequences retriving from the input FASTA (nucleotide and proteins) file into two distinct files based on a tunable, user-defined sequence length, as well as the plots or dynamic visualizations of the corresponding sequences.Availability and implementationThe detailed SeqLengthPlot pipeline is available on GitHub athttps://github.com/danydguezperez/SeqLengthPlot, released under the GPL-3.0 license. Additional datasets used as sources or compiled as use cases are publicy available through the Mendeley Data repository:DATASET_Ss_SE.1:http://dx.doi.org/10.17632/pmxwfjyyvy.1,DATASET_Ss_SE.2:http://dx.doi.org/10.17632/3rtbr7c9s8.1,DATASET_Ss_SE.3:http://dx.doi.org/10.17632/wn5kbk5ryy.1,DATASET_Ss_SE.4:http://dx.doi.org/10.17632/sh79mdcm2c.1andDATASET_Ss_SE.5:http://dx.doi.org/10.17632/zmvvff35dx.1.
A Constitutive Heterochromatic Region Shapes Genome Organization and Impacts Gene Expression inNeurospora crassa
Authors: Reckard Andrew T. , Pandeya Abhishek , Voris Jacob M. , Gonzalez Cruz Carlos G. , Oluwadare Oluwatosin , Klocko Andrew D. 
Published: June 2024

AbstractBackgroundOrganization of the eukaryotic genome is essential for proper function, including gene expression. In metazoans, chromatin loops and Topologically Associated Domains (TADs) organize genes into transcription factories, while chromosomes occupy nuclear territories in which silent heterochromatin is compartmentalized at the nuclear periphery and active euchromatin localizes to the nucleus center. A similar hierarchical organization occurs in the fungus Neurospora crassa where its seven chromosomes form a Rabl conformation typified by heterochromatic centromeres and telomeres independently clustering at the nuclear membrane, while interspersed heterochromatic loci aggregate across Megabases of linear genomic distance to loop chromatin in TAD-like structures. However, the role of individual heterochromatic loci in normal genome organization and function is unknown.ResultsWe examined the genome organization of a Neurospora strain harboring a ∼47.4 kilobase deletion within a temporarily silent, facultative heterochromatic region, as well as the genome organization of a strain deleted of a 110.6 kilobase permanently silent constitutive heterochromatic region. While the facultative heterochromatin deletion minimally effects local chromatin structure or telomere clustering, the constitutive heterochromatin deletion alters local chromatin structure, the predicted three-dimensional chromosome conformation, and the expression of some genes, which are qualitatively repositioned into the nucleus center, while increasing Hi-C variability.ConclusionsOur work elucidates how an individual constitutive heterochromatic region impacts genome organization and function. Specifically, one silent region indirectly assists in the hierarchical folding of the entire Neurospora genome by aggregating into the “typical” heterochromatin bundle normally observed in wild type nuclei, which may promote normal gene expression by positioning euchromatin in the nucleus center.
α-Synuclein Overexpression and the Microbiome Shape the Gut and Brain Metabolome in Mice
Authors: Morais Livia H. , Boktor Joseph C. , MahmoudianDehkordi Siamak , Kaddurah-Daouk Rima , Mazmanian Sarkis K. 
Published: June 2024

AbstractPathological forms of the protein α-synuclein contribute to a family of disorders termed synucleinopathies, which includes Parkinson’s disease (PD). Most cases of PD are believed to arise from gene-environment interactions. Microbiome composition is altered in PD, and gut bacteria are causal to symptoms and pathology in animal models. To explore how the microbiome may impact PD-associated genetic risks, we quantitatively profiled nearly 630 metabolites from 26 biochemical classes in the gut, plasma, and brain of α-synuclein-overexpressing (ASO) mice with or without microbiota. We observe tissue-specific changes driven by genotype, microbiome, and their interaction. Many differentially expressed metabolites in ASO mice are also dysregulated in human PD patients, including amine oxides, bile acids and indoles. Notably, levels of the microbial metabolite trimethylamine N-oxide (TMAO) strongly correlate from the gut to the plasma to the brain, identifying a product of gene-environment interactions that may influence PD-like outcomes in mice. TMAO is elevated in the blood and cerebral spinal fluid of PD patients. These findings uncover broad metabolomic changes that are influenced by the intersection of host genetics and the microbiome in a mouse model of PD.