bluuebunny/crossref_metadata_2025_split huggingface dataset:
tRForest: a novel random forest-based algorithm for tRNA-derived fragment target prediction
Authors: Parikh Rohan , Wilson Briana , Marrah Laine , Su Zhangli , Saha Shekhar , Kumar Pankaj , Huang Fenix , Dutta Anindya 
Published: December 2021

AbstracttRNA fragments (tRFs) are small RNAs comparable to the size and function of miRNAs. tRFs are generally Dicer independent, are found associated with Ago, and can repress expression of genes post-transcriptionally. Given that this expands the repertoire of small RNAs capable of post-transcriptional gene expression, it is important to predict tRF targets with confidence. Some attempts have been made to predict tRF targets, but are limited in the scope of tRF classes used in prediction or limited in feature selection. We hypothesized that established miRNA target prediction features applied to tRFs through a random forest machine learning algorithm will immensely improve tRF target prediction. Using this approach, we show significant improvements in tRF target prediction for all classes of tRFs and validate our predictions in two independent cell lines. Finally, Gene Ontology analysis suggests that among the tRFs conserved between mice and humans, the predicted targets are enriched significantly in neuronal function, and we show this specifically for tRF-3009a. These improvements to tRF target prediction further our understanding of tRF function broadly across species and provide avenues for testing novel roles for tRFs in biology. We have created a publicly available website for the targets of tRFs predicted by tRForest.
Glutathione binding to the plant AtAtm3 transporter and implications for the conformational coupling of ABC transporters
Authors: Fan Chengcheng , Rees Douglas C. 
Published: December 2021

AbstractThe ATP Binding Cassette (ABC) transporter of mitochondria (Atm) from Arabidopsis thaliana (AtAtm3) has been implicated in the maturation of cytosolic iron-sulfur proteins and heavy metal detoxification, plausibly by exporting glutathione derivatives. Using single-particle cryo-electron microscopy, we have determined structures of AtAtm3 in multiple conformational states. These structures not only provide a structural framework for defining the alternating access transport cycle, but also highlight an unappreciated feature of the glutathione binding site, namely the paucity of cysteine residues that could potentially form inhibitory mixed disulfides with glutathione. Despite extensive efforts, we were unable to prepare the ternary complex of AtAtm3 with bound GSSG and MgATP. A survey of structurally characterized type IV ABC transporters that includes AtAtm3 establishes that while nucleotides are found associated with all conformational states, they are effectively required to stabilize occluded and outward-facing conformations. In contrast, transport substrates have only been observed associated with inward-facing conformations. The absence of structures containing both nucleotide and transport substrate suggests that this ternary complex exists only transiently during the transport cycle.
ProteinGLUE: A multi-task benchmark suite for self-supervised protein modeling
Authors: Capel Henriette , Weiler Robin , Dijkstra Maurits , Vleugels Reinier , Bloem Peter , Feenstra K. Anton 
Published: December 2021

ABSTRACTSelf-supervised language modeling is a rapidly developing approach for the analysis of protein sequence data. However, work in this area is heterogeneous and diverse, making comparison of models and methods difficult. Moreover, models are often evaluated only on one or two downstream tasks, making it unclear whether the models capture generally useful properties. We introduce the ProteinGLUE benchmark for the evaluation of protein representations: a set of seven tasks for evaluating learned protein representations. We also offer reference code, and we provide two baseline models with hyperparameters specifically trained for these benchmarks.Pre-training was done on two tasks, masked symbol prediction and next sentence prediction. We show that pre-training yields higher performance on a variety of downstream tasks such as secondary structure and protein interaction interface prediction, compared to no pre-training. However, the larger base model does not outperform the smaller medium. We expect the ProteinGLUE benchmark dataset introduced here, together with the two baseline pre-trained models and their performance evaluations, to be of great value to the field of protein sequence-based property prediction.Availabilitycode and datasets from https://github.com/ibivu/protein-glue
A library for fMRI real-time processing systems in python (RTPSpy) with comprehensive online noise reduction, fast and accurate anatomical image processing, and online processing simulation
Authors: Misaki Masaya , Bodurka Jerzy , Paulus Martin P 
Published: December 2021

AbstractReal-time fMRI (rtfMRI)has enormous potential for both mechanistic brain imaging studies or treatment-oriented neuromodulation. However, the adaption of rtfMRI has been limited due to technical difficulties implement an efficient computational framework. Here, we introduce a python library for real-time fMRI (rtfMRI) data processing systems, Real-Time Processing System in python (RTPSpy), to provide building blocks for a custom rtfMRI application with extensive and advanced functionalities. RTPSpy is a library package including 1) a fast, comprehensive, and flexible online fMRI image processing modules comparable to offline denoising, 2) utilities for fast and accurate anatomical image processing to define an anatomical target region, 3) a simulation system of online fMRI processing to optimize a pipeline and target signal calculation, 4) simple interface to an external application for feedback presentation, and 5) a boilerplate graphical user interface (GUI) integrating operations with RTPSpy library. The fast and accurate anatomical image processing utility wraps external tools, including FastSurfer, ANTs, and AFNI, to make tissue segmentation and region of interest masks. We confirmed that the quality of the output masks was comparable with FreeSurfer, and the anatomical image processing could complete in a few minutes. The modular nature of RTPSpy provides the ability to use it for a simulation analysis to optimize a processing pipeline and target signal calculation. We present a sample script for building a real-time processing pipeline and running a simulation using RTPSpy. The library also offers a simple signal exchange mechanism with an external application using a TCP/IP socket. While the main components of the RTPSpy are the library modules, we also provide a GUI class for easy access to the RTPSpy functions. The boilerplate GUI application provided with the package allows users to develop a customized rtfMRI application with minimum scripting labor. The limitations of the package as it relates to environment-specific implementations are discussed. These library components can be customized and can be used in parts. Taken together, RTPSpy is an efficient and adaptable option for developing rtfMRI applications. The package is available from GitHub (https://github.com/mamisaki/RTPSpy) with GPL3 license.
GiantStarshipelements mobilize accessory genes in fungal genomes
Authors: Gluck-Thaler Emile , Ralston Timothy , Konkel Zachary , Ocampos Cristhian Grabowski , Ganeshan Veena Devi , Dorrance Anne E. , Niblack Terry L. , Wood Corlett W. , Slot Jason C. , Lopez-Nicora Horacio D. , Vogan Aaron A. 
Published: December 2021

AbstractAccessory genes are variably present among members of a species and are a reservoir of adaptive functions. In bacteria, differences in gene distributions among individuals largely result from mobile elements that acquire and disperse accessory genes as cargo. In contrast, the impact of cargo-carrying elements on eukaryotic evolution remains largely unknown. Here, we show that variation in genome content within multiple fungal species is facilitated byStarships,a novel group of massive mobile elements that are 110 kb long on average, share conserved components, and carry diverse arrays of accessory genes. We identified hundreds ofStarship-like regions across every major class of filamentous Ascomycetes, including 28 distinctStarshipsthat range from 27-393 kb and last shared a common ancestor ca. 400 mya. Using new long-read assemblies of the plant pathogenMacrophomina phaseolina, we characterize 4 additionalStarshipswhose past and ongoing activities contribute to standing variation in genome structure and content. One of these elements,Voyager, inserts into 5S rDNA and contains a candidate virulence factor whose increasing copy number has contrasting associations with pathogenic and saprophytic growth, suggestingVoyager’s activity underlies an ecological trade-off. We propose thatStarshipsare eukaryotic analogs of bacterial integrative and conjugative elements based on parallels between their conserved components and may therefore represent the first known agents of active gene transfer in eukaryotes. Our results suggest thatStarshipshave shaped the content and structure of fungal genomes for millions of years and reveal a new concerted route for evolution throughout an entire eukaryotic phylum.
Single-cell multi-omic velocity infers dynamic and decoupled gene regulation
Authors: Li Chen , Virgilio Maria , Collins Kathleen L. , Welch Joshua D. 
Published: December 2021

AbstractSingle-cell multi-omic datasets, in which multiple molecular modalities are profiled within the same cell, provide a unique opportunity to discover the relationships between cellular epigenomic and transcriptomic changes. To realize this potential, we developed MultiVelo, a mechanistic model of gene expression that extends the RNA velocity framework to incorporate epigenomic data. MultiVelo uses a probabilistic latent variable model to estimate the switch time and rate parameters of chromatin accessibility and gene expression from single-cell data, providing a quantitative summary of the temporal relationship between epigenomic and transcriptomic changes. Incorporating chromatin accessibility data significantly improves the accuracy of cell fate prediction compared to velocity estimates from RNA only. Fitting MultiVelo on single-cell multi-omic datasets from brain, skin, and blood cells reveals two distinct classes of genes distinguished by whether chromatin closes before or after transcription ceases. Our model also identifies four types of cell states–two states in which epigenome and transcriptome are coupled and two distinct decoupled states. The parameters inferred by MultiVelo quantify the length of time for which genes occupy each of the four states, ranking genes by the degree of coupling between transcriptome and epigenome. Finally, we identify time lags between transcription factor expression and binding site accessibility and between disease-associated SNP accessibility and expression of the linked genes. We provide an open-source Python implementation of MultiVelo on PyPI and GitHub (https://github.com/welch-lab/MultiVelo).
Potential cross-protection against SARS-CoV-2 from previous exposure to bovine coronavirus
Authors: Querne Lana Bazan Peters , Bastos Fernanda Zettel , Beirão Breno Castello Branco 
Published: December 2021

AbstractHumans have long shared infectious agents with cattle, and the common cold OC-43 CoV is a not-so-distant example of cross-species viral spillover. Human exposure to BCoV is certainly common, as the virus is endemic in cattle-raising regions. This article shows an in silico investigation of shared viral epitopes between BCoV and SARS-CoV-2. HLA recognition and lymphocyte reactivity were assessed using freely-available resources. Several epitopes were shared between BCoV and SARS-CoV-2, both for B and T lymphocytes. These data demonstrate that possible cross-protection is being induced by human exposure to cattle.
Genomic landscape, polymorphism and possible LINE-associated delivery of G-Quadruplex motifs in the bovine genes
Authors: Stefos Georgios C. , Theodorou Georgios , Politis Ioannis 
Published: December 2021

ABSTRACTG-Quadruplex structures are non-B DNA structures that occur in regions carrying short runs of guanines. They are implicated in several biological processes including transcription, translation, replication and telomere maintenance as well as in several pathological conditions like cancer and thus they have gained the attention of the scientific community. The rise of the –omics era significantly affected the G-quadruplex research and the genome-wide characterization of G-Quadruplexes has been rendered a necessary first step towards applying genomics approaches for their study. While in human and several model organisms there is a considerable number of works studying genome-wide the DNA motifs with potential to form G-quadruplexes (G4-motifs), there is a total absence of any similar studies regarding livestock animals. The objectives of the present study were to provide a detailed characterization of the bovine genic G4-motifs’ distribution and properties and to suggest a possible mechanism for the delivery of G4 motifs in the genes. Our data indicate that the distribution of G4s within bovine genes and the annotation of said genes to Gene Ontology terms are similar to what is already shown for other organisms. By investigating their structural characteristics and polymorphism, it is obvious that the overall stability of the putative quadruplex structures is in line with the current notion in the G4 field. Similarly to human, the bovine G4s are overrepresented in specific LINE repeat elements, the L1_BTs in the case of cattle. We suggest these elements as vehicles for delivery of G4 motifs in the introns of the bovine genes. Lastly, it seems that a basis exists for connecting traits of agricultural importance to the genetic variation of G4 motifs, thus, cattle could become an interesting new model organism for G4-related genetic studies.
Nanoscale details of mitochondrial fission revealed by cryo-electron tomography
Authors: Mageswaran Shrawan Kumar , Grotjahn Danielle Ann , Zeng Xiangrui , Barad Benjamin Asher , Medina Michaela , Hoang My Hanh , Dobro Megan J , Chang Yi-Wei , Xu Min , Yang Wei Yuan , Jensen Grant J. 
Published: December 2021

AbstractMitochondrial fission is required for proper segregation during cell division, quality control, and cellular homeostasis (metabolism and energy production). Despite its importance, models of the process remain speculative. Here we apply cryogenic electron tomography to image the nanoscale architecture of mitochondrial fission in mammalian cells. We find that constriction of the inner and outer membranes is coordinated, suggesting that force on both membranes is applied externally. While we observe ER at constriction sites, it did not encircle constrictions. Instead, we find long bundles of both unbranched actin and septin filaments enriched at constrictions. Actin bundles align with the central region of division bridges and septin bundles with the necks on either side. Septin bundles appear to guide microtubules to constriction sites, suggesting, along with autolysosomes observed in the vicinity, a pathway for mitophagy. Together, our results rule out several existing models for mitochondrial fission and provide empirical parameters to inform the development of realistic coarse-grained models in the future.
Determining Risk Factors for Triple Whammy Acute Kidney Injury
Authors: Leete Jessica , Wang Carolyn , López-Hernández Francisco J. , Layton Anita T. 
Published: December 2021

AbstractConcurrent use of a diuretic, a renin-angiotensin system (RAS) inhibitor, and a non-steroidal anti-inflammatory drug (NSAID) significantly increases the risk of acute kidney injury (AKI). This phenomenon is known as “triple whammy”. Diuretics and RAS inhibitors, such as an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, are often prescribed in tandem for the treatment of hypertension, whereas some NSAIDs, such as ibuprofen, are available over the counter. As such, concurrent treatment with all three drugs is common. The goals of this study are to better understand the mechanisms underlying the development of triple whammy AKI and to identify physiological factors that may increase an individual’s susceptibility. To accomplish these goals, we utilize computational models of long-term blood pressure regulation. These models include variables describing the heart and circulation, kidney function, sodium and water reabsorption in the nephron and the RAS and are parameterized separately for men and women. Hypertension is modeled as overactive renal sympathetic nervous activity. Model simulations suggest that individual variations in water intake, the myogenic response, and drug sensitivity may predispose patients with hypertension to develop triple whammy-induced AKI.
Chemical-induced Gene Expression Ranking and its Application to Pancreatic Cancer Drug Repurposing
Authors: Pham Thai-Hoang , Qiu Yue , Liu Jiahui , Zimmer Steven , O’Neill Eric , Xie Lei , Zhang Ping 
Published: December 2021

ABSTRACTChemical-induced gene expression profiles provide critical information on the mode of action, off-target effect, and cellar heterogeneity of chemical actions in a biological system, thus offer new opportunities for drug discovery, system pharmacology, and precision medicine. Despite their successful applications in drug repurposing, large-scale analysis that leverages these profiles is limited by sparseness and low throughput of the data. Several methods have been proposed to predict missing values in gene expression data. However, most of them focused on imputation and classification settings which have limited applications to real-world scenarios of drug discovery. Therefore, a new deep learning framework named chemical-induced gene expression ranking (CIGER) is proposed to target a more realistic but more challenging setting in which the model predicts the rankings of genes in the whole gene expression profiles induced byde novochemicals. The experimental results show that CIGER significantly outperforms existing methods in both ranking and classification metrics for this prediction task. Furthermore, a new drug screening pipeline based on CIGER is proposed to select approved or investigational drugs for the potential treatments of pancreatic cancer. Our predictions have been validated by experiments, thereby showing the effectiveness of CIGER for phenotypic compound screening of precision drug discovery in practice.
GREPore-seq: A Robust Workflow to Detect Changes after Gene Editing through Long-range PCR and Nanopore Sequencing
Authors: Quan Zi-Jun , Li Si-Ang , Yang Zhi-Xue , Zhao Juan-Juan , Li Guo-Hua , Zhang Feng , Wen Wei , Cheng Tao , Zhang Xiao-Bing 
Published: December 2021

AbstractTo achieve the enormous potential of gene-editing technology in clinical therapies, both the on-target and unintended editing consequences need to be thoroughly evaluated. However, there is a lack of a comprehensive, pipelined, large-scale and economical workflow for detecting genome editing outcomes, in particular insertion or deletion of a large fragment. Here, we describe an approach for efficient and accurate detection of multiple genetic changes after CRISPR-Cas9 editing by pooled nanopore sequencing of barcoded long-range PCR products. To overcome the high error rates and indels of nanopore sequencing, we developed a pipeline to capture the barcoded sequences by grepping reads of nanopore amplicon sequencing (GREPore-seq). GREPore-seq can detect NHEJ-mediated double-stranded oligodeoxynucleotide (dsODN) insertions with comparable accuracy to Illumina next-generation sequencing (NGS). GREPore-seq also identifies HDR-mediated large gene knock-in, which excellently correlates with FACS analysis data. Low-level plasmid backbone insertion after HDR editing was also detected. We have established a practical workflow to identify genetic changes, including quantifying dsODN insertions, knock-ins, plasmid backbone insertions, and large fragment deletions after CRISPR editing. This toolkit for nanopore sequencing of pooled long amplicons should have broad applications in assessing on-target HDR editing and inadvertent large indels of over 1 kb. GREPore-seq is freely available at GitHub (https://github.com/lisiang/GREPore-seq).
SBP-SITA: A sequence-based prediction tool for S-itaconation
Authors: Zhang Laizhi , Wang Xuanwen , Zhang Lin , Meng Yanzheng , Wang Ziyu , Chen Yu , Li Lei 
Published: December 2021

AbstractAs a recently-reported post-translational modification, S-itaconation plays an important role in inflammation suppression. In order to understand its regulatory mechanism in many life activities, the essential step is the recognition of S-itaconation. However, it is difficult to identify S-itaconation in the proteome for the high cost, which limits further investigation. In this study, we constructed an ensemble algorithm based on Soft Voting Classifier. The area under the ROC curve (AUC) value 0.73 for ensemble model. Accordingly, we constructed the on-line prediction tool dubbed SBP-SITA for easily identifying Cystine sites. SBP-SITA is available at http://www.bioinfogo.org/sbp-sita.
Simulated colonic fluid replicates the in vivo growth capabilities of Citrobacter rodentium mutants and highlights a critical role for the Cpx envelope stress response in mediating stressors encountered in the gastrointestinal tract
Authors: Gilliland Ashley , Gavino Christina , Gruenheid Samantha , Raivio Tracy 
Published: December 2021

AbstractCitrobacter rodentium is an attaching and effacing (A/E) pathogen used as a model for enteropathogenic and enterohemorrhagic Escherichia coli infections in mice. While in the host, C. rodentium must adapt to stresses in the gastrointestinal tract such as antimicrobial peptides, pH changes, and bile salts. The Cpx envelope stress response (ESR) is a two-component system used by some bacteria to remediate stress by modulating gene expression and is necessary for C. rodentium pathogenesis in mice. To investigate genes in the Cpx regulon that may contribute to C. rodentium pathogenesis, RNA-Seq, SILAC, and microarray data from previous research was mined and the genes yebE, ygiB, bssR, and htpX were confirmed to be strongly upregulated by the presence of CpxRA using lux reporter constructs. To determine the function of these genes in vivo, knockout mutants were tested in C57Bl/6J and C3H/HeJ mice. Although none of the mutants exhibited marked virulence phenotypes, the ΔcpxRA mutant had reduced colonization and attenuated virulence, as previously determined. We also found that the absence of the Cpx ESR resulted in higher expression of the LEE master regulator, ler. In addition, we determined that the ΔcpxRA mutant had a growth defect in medium simulating the colon, as did several of the mutants bearing deletions in Cpx-upregulated genes. Overall, these results indicate that the ΔcpxRA virulence defect is not due to any single Cpx regulon gene examined. Instead, attenuation may be the result of defective growth in the colonic environment resulting from the collective impact of multiple Cpx-regulated genes.