bluuebunny/crossref_metadata_2025_split huggingface dataset:
SPServer: split-statistical potentials for the analysis of protein structures and protein–protein interactions
Authors: Aguirre-Plans Joaquim , Meseguer Alberto , Molina-Fernandez Ruben , Marín-López Manuel Alejandro , Jumde Gaurav , Casanova Kevin , Bonet Jaume , Fornes Oriol , Fernandez-Fuentes Narcis , Oliva Baldo 
Published: January 2021

AbstractBackgroundStatistical potentials, also named knowledge-based potentials, are scoring functions derived from empirical data that can be used to evaluate the quality of protein folds and protein–protein interaction (PPI) structures. In previous works we decomposed the statistical potentials in different terms, named Split-Statistical Potentials, accounting for the type of amino acid pairs, their hydrophobicity, solvent accessibility and type of secondary structure. These potentials have been successfully used to identify near-native structures in protein structure prediction, rank protein docking poses, and predict PPI binding affinities.ResultsHere, we present the SPServer, a web server that applies the Split-Statistical Potentials to analyze protein folds and protein interfaces. SPServer provides global scores as well as residue/residue-pair profiles presented as score plots and maps. This level of detail allows users to: (1) identify potentially problematic regions on protein structures; (2) identify disrupting amino acid pairs in protein interfaces; and (3) compare and analyze the quality of tertiary and quaternary structural models.ConclusionsWhile there are many web servers that provide scoring functions to assess the quality of either protein folds or PPI structures, SPServer integrates both aspects in a unique easy-to-use web server. Moreover, the server permits to locally assess the quality of the structures and interfaces at a residue level and provides tools to compare the local assessment between structures.Server addresshttps://sbi.upf.edu/spserver/.
MicrobeAnnotator: a user-friendly, comprehensive functional annotation pipeline for microbial genomes
Authors: Ruiz-Perez Carlos A. , Conrad Roth E. , Konstantinidis Konstantinos T. 
Published: January 2021

Abstract
Background
High-throughput sequencing has increased the number of available microbial genomes recovered from isolates, single cells, and metagenomes. Accordingly, fast and comprehensive functional gene annotation pipelines are needed to analyze and compare these genomes. Although several approaches exist for genome annotation, these are typically not designed for easy incorporation into analysis pipelines, do not combine results from different annotation databases or offer easy-to-use summaries of metabolic reconstructions, and typically require large amounts of computing power for high-throughput analysis not available to the average user.

Results
Here, we introduce MicrobeAnnotator, a fully automated, easy-to-use pipeline for the comprehensive functional annotation of microbial genomes that combines results from several reference protein databases and returns the matching annotations together with key metadata such as the interlinked identifiers of matching reference proteins from multiple databases [KEGG Orthology (KO), Enzyme Commission (E.C.), Gene Ontology (GO), Pfam, and InterPro]. Further, the functional annotations are summarized into Kyoto Encyclopedia of Genes and Genomes (KEGG) modules as part of a graphical output (heatmap) that allows the user to quickly detect differences among (multiple) query genomes and cluster the genomes based on their metabolic similarity. MicrobeAnnotator is implemented in Python 3 and is freely available under an open-source Artistic License 2.0 from https://github.com/cruizperez/MicrobeAnnotator.

Conclusions
We demonstrated the capabilities of MicrobeAnnotator by annotating 100 Escherichia coli and 78 environmental Candidate Phyla Radiation (CPR) bacterial genomes and comparing the results to those of other popular tools. We showed that the use of multiple annotation databases allows MicrobeAnnotator to recover more annotations per genome compared to faster tools that use reduced databases and is computationally efficient for use in personal computers. The output of MicrobeAnnotator can be easily incorporated into other analysis pipelines while the results of other annotation tools can be seemingly incorporated into MicrobeAnnotator to generate summary plots.
MATHLA: a robust framework for HLA-peptide binding prediction integrating bidirectional LSTM and multiple head attention mechanism
Authors: Ye Yilin , Wang Jian , Xu Yunwan , Wang Yi , Pan Youdong , Song Qi , Liu Xing , Wan Ji 
Published: January 2021

AbstractBackgroundAccurate prediction of binding between class I human leukocyte antigen (HLA) and neoepitope is critical for target identification within personalized T-cell based immunotherapy. Many recent prediction tools developed upon the deep learning algorithms and mass spectrometry data have indeed showed improvement on the average predicting power for class I HLA-peptide interaction. However, their prediction performances show great variability over individual HLA alleles and peptides with different lengths, which is particularly the case for HLA-C alleles due to the limited amount of experimental data. To meet the increasing demand for attaining the most accurate HLA-peptide binding prediction for individual patient in the real-world clinical studies, more advanced deep learning framework with higher prediction accuracy for HLA-C alleles and longer peptides is highly desirable.ResultsWe present a pan-allele HLA-peptide binding prediction framework—MATHLA which integrates bi-directional long short-term memory network and multiple head attention mechanism. This model achieves better prediction accuracy in both fivefold cross-validation test and independent test dataset. In addition, this model is superior over existing tools regarding to the prediction accuracy for longer ligand ranging from 11 to 15 amino acids. Moreover, our model also shows a significant improvement for HLA-C-peptide-binding prediction. By investigating multiple-head attention weight scores, we depicted possible interaction patterns between three HLA I supergroups and their cognate peptides.ConclusionOur method demonstrates the necessity of further development of deep learning algorithm in improving and interpreting HLA-peptide binding prediction in parallel to increasing the amount of high-quality HLA ligandome data.
Reduced translation efficiency due to novel splicing variants in 5′ untranslated region and identification of novel cis-regulatory elements in canine and human BRCA2
Authors: Yoshikawa Yasunaga , Kozuma Hajime , Morimatsu Masami , Sugawara Kaori , Orino Koichi 
Published: January 2021

Abstract
Background
Breast cancer 2, early onset (BRCA2) is a tumor suppressor gene. The protein encoded by this gene plays an important role in homologous recombination (HR)-mediated DNA repair. Deleterious mutations in BRCA2 and downregulation of its expression have been associated with tumorigenesis in dogs and humans. Thus, regulation of BRCA2 expression level is important for maintaining homeostasis in homologous recombination.

Results
In this study, the mechanisms that regulate the expression of BRCA2 were proposed. Novel splicing variants were identified in the 5′ untranslated region (UTR) of canine and human BRCA2 in canine testis, canine ovary, and canine and human cultured cell lines. In cultured cells, the ratio of BRCA2 splicing variants at the 5′ UTR was altered by serum starvation. These novel splicing variants, excluding one of the canine splicing variants, were found to reduce the translational efficiency. Additionally, the DNA sequence in human BRCA2 intron 1 harbored novel cis-regulatory elements. Three silencer and two enhancer cis-regulatory elements were identified in human BRCA2 intron 1.

Conclusions
This study demonstrates that BRCA2 expression level is regulated via 5′ UTR splicing variants and that the BRCA2 intron 1 region harbors cis-regulatory elements.
A novel method for isolation and culture of primary swine gastric epithelial cells
Authors: Bautista-Amorocho Henry , Silva-Sayago Jorge Alexander , Goyeneche-Patino Diego A. , Pérez-Cala Tania Liseth , Macías-Gómez Fabio , Arango-Viana Juan Carlos , Martínez Alonso 
Published: January 2021

Abstract
Background
Culturing primary epithelial cells has a major advantage over tumor-derived or immortalized cell lines as long as their functional phenotype and genetic makeup are mainly maintained. The swine model has shown to be helpful and reliable when used as a surrogate model for human diseases. Several porcine cell lines have been established based on a variety of tissues, which have shown to extensively contribute to the current understanding of several pathologies, especially cancer. However, protocols for the isolation and culture of swine gastric epithelial cells that preserve cell phenotype are rather limited. We aimed to develop a new method for establishing a primary epithelial cell culture from the fundic gland region of the pig stomach.

Results
Mechanical and enzymatic dissociation of gastric tissue was possible by combining collagenase type I and dispase II, protease inhibitors and antioxidants, which allowed the isolation of epithelial cells from the porcine fundic glands showing cell viability > 90% during the incubation period. Gastric epithelial cells cultured in RPMI 1640, DMEM-HG and DMEM/F12 media did not contribute enough to cell adhesion, cluster formation and cell proliferation. By contrast, William’s E medium supplemented with growth factors supports confluency and proliferation of a pure epithelial cell monolayer after 10 days of incubation at 37 °C, 5% CO2. Mucin-producing cell phenotype of primary isolates was confirmed by PAS staining, MUC1 by immunohistochemistry, as well as the expression of MUC1 and MUC20 genes by RT-PCR and cDNA sequencing. Swine gastric epithelial cells also showed origin-specific markers such as cytokeratin cocktail (AE1/AE3) and cytokeratin 18 (CK-18) using immunohistochemical and immunofluorescence methods, respectively.

Conclusions
A new method was successfully established for the isolation of primary gastric epithelial cells from the fundic gland zone through a swine model based on a combination of tissue-specific proteases, protease inhibitors and antioxidants after mechanical cell dissociation. The formulation of William’s E medium with growth factors for epithelial cells contributes to cell adhesion and preserves functional primary cells phenotype, which is confirmed by mucin production and expression of typical epithelial markers over time.
ATAC-Seq identifies regions of open chromatin in the bronchial lymph nodes of dairy calves experimentally challenged with bovine respiratory syncytial virus
Authors: Johnston Dayle , Kim JaeWoo , Taylor Jeremy F. , Earley Bernadette , McCabe Matthew S. , Lemon Ken , Duffy Catherine , McMenamy Michael , Cosby S. Louise , Waters Sinéad M. 
Published: January 2021

AbstractBackgroundBovine Respiratory Syncytial Virus (BRSV) is a cause of Bovine Respiratory Disease (BRD). DNA-based biomarkers contributing to BRD resistance are potentially present in non-protein-coding regulatory regions of the genome, which can be determined using ATAC-Seq. The objectives of this study were to: (i) identify regions of open chromatin in DNA extracted from bronchial lymph nodes (BLN) of healthy dairy calves experimentally challenged with BRSV and compare them with those from non-challenged healthy control calves, (ii) elucidate the chromatin regions that were differentially or uniquely open in the BRSV challenged relative to control calves, and (iii) compare the genes found in regions proximal to the differentially open regions to the genes previously found to be differentially expressed in the BLN in response to BRSV and to previously identified BRD susceptibility loci. This was achieved by challenging clinically healthy Holstein-Friesian calves (mean age 143 ± 14 days) with either BRSV inoculum (n = 12) or with sterile phosphate buffered saline (PBS) (n = 6) and preparing and sequencing ATAC-Seq libraries from fresh BLN tissues.ResultsUsing Diffbind, 9,144 and 5,096 differentially accessible regions (P < 0.05, FDR < 0.05) were identified between BRSV challenged and control calves employing DeSeq2 and EdgeR, respectively. Additionally, 8,791 chromatin regions were found to be uniquely open in BRSV challenged calves. Seventy-six and 150 of the genes that were previously found to be differentially expressed using RNA-Seq, were located within 2 kb downstream of the differentially accessible regions, and of the regions uniquely open in BRSV challenged calves, respectively. Pathway analyses within ClusterProfiler indicated that these genes were involved in immune responses to infection and participated in the Th1 and Th2 pathways, pathogen recognition and the anti-viral response. There were 237 differentially accessible regions positioned within 40 previously identified BRD susceptibility loci.ConclusionsThe identified open chromatin regions are likely to be involved in the regulatory response of gene transcription induced by infection with BRSV. Consequently, they may contain variants which impact resistance to BRD that could be used in breeding programmes to select healthier, more robust cattle.
Genome-wide identification and characterization of long non-coding RNAs conferring resistance to Colletotrichum gloeosporioides in walnut (Juglans regia)
Authors: Feng Shan , Fang Hongcheng , Liu Xia , Dong Yuhui , Wang Qingpeng , Yang Ke Qiang 
Published: January 2021

Abstract
Background
Walnut anthracnose caused by Colletotrichum gloeosporioides (Penz.) Penz. and Sacc. is an important walnut production problem in China. Although the long non-coding RNAs (lncRNAs) are important for plant disease resistance, the molecular mechanisms underlying resistance to C. gloeosporioides in walnut remain poorly understood.

Results
The anthracnose-resistant F26 fruits from the B26 clone and the anthracnose-susceptible F423 fruits from the 4–23 clone of walnut were used as the test materials. Specifically, we performed a comparative transcriptome analysis of F26 and F423 fruit bracts to identify differentially expressed LncRNAs (DELs) at five time-points (tissues at 0 hpi, pathological tissues at 24 hpi, 48 hpi, 72 hpi, and distal uninoculated tissues at 120 hpi). Compared with F423, a total of 14,525 DELs were identified, including 10,645 upregulated lncRNAs and 3846 downregulated lncRNAs in F26. The number of upregulated lncRNAs in F26 compared to in F423 was significantly higher at the early stages of C. gloeosporioides infection. A total of 5 modules related to disease resistance were screened by WGCNA and the target genes of lncRNAs were obtained. Bioinformatic analysis showed that the target genes of upregulated lncRNAs were enriched in immune-related processes during the infection of C. gloeosporioides, such as activation of innate immune response, defense response to bacterium, incompatible interaction and immune system process, and enriched in plant hormone signal transduction, phenylpropanoid biosynthesis and other pathways. And 124 known target genes for 96 hub lncRNAs were predicted, including 10 known resistance genes. The expression of 5 lncRNAs and 5 target genes was confirmed by qPCR, which was consistent with the RNA-seq data.

Conclusions
The results of this study provide the basis for future functional characterizations of lncRNAs regarding the C. gloeosporioides resistance of walnut fruit bracts.
Chromatin loop anchors contain core structural components of the gene expression machinery in maize
Authors: Deschamps Stéphane , Crow John A. , Chaidir Nadia , Peterson-Burch Brooke , Kumar Sunil , Lin Haining , Zastrow-Hayes Gina , May Gregory D. 
Published: January 2021

Abstract
Background
Three-dimensional chromatin loop structures connect regulatory elements to their target genes in regions known as anchors. In complex plant genomes, such as maize, it has been proposed that loops span heterochromatic regions marked by higher repeat content, but little is known on their spatial organization and genome-wide occurrence in relation to transcriptional activity.

Results
Here, ultra-deep Hi-C sequencing of maize B73 leaf tissue was combined with gene expression and open chromatin sequencing for chromatin loop discovery and correlation with hierarchical topologically-associating domains (TADs) and transcriptional activity. A majority of all anchors are shared between multiple loops from previous public maize high-resolution interactome datasets, suggesting a highly dynamic environment, with a conserved set of anchors involved in multiple interaction networks. Chromatin loop interiors are marked by higher repeat contents than the anchors flanking them. A small fraction of high-resolution interaction anchors, fully embedded in larger chromatin loops, co-locate with active genes and putative protein-binding sites. Combinatorial analyses indicate that all anchors studied here co-locate with at least 81.5% of expressed genes and 74% of open chromatin regions. Approximately 38% of all Hi-C chromatin loops are fully embedded within hierarchical TAD-like domains, while the remaining ones share anchors with domain boundaries or with distinct domains. Those various loop types exhibit specific patterns of overlap for open chromatin regions and expressed genes, but no apparent pattern of gene expression. In addition, up to 63% of all unique variants derived from a prior public maize eQTL dataset overlap with Hi-C loop anchors. Anchor annotation suggests that < 7% of all loops detected here are potentially devoid of any genes or regulatory elements. The overall organization of chromatin loop anchors in the maize genome suggest a loop modeling system hypothesized to resemble phase separation of repeat-rich regions.

Conclusions
Sets of conserved chromatin loop anchors mapping to hierarchical domains contains core structural components of the gene expression machinery in maize. The data presented here will be a useful reference to further investigate their function in regard to the formation of transcriptional complexes and the regulation of transcriptional activity in the maize genome.
Genome-wide identification and characterization of small auxin-up RNA (SAUR) gene family in plants: evolution and expression profiles during normal growth and stress response
Authors: Zhang Hao , Yu Zhenjia , Yao Xiaodie , Chen Jingli , Chen Xing , Zhou Huiwen , Lou Yuxia , Ming Feng , Jin Yue 
Published: January 2021

AbstractBackgroundAuxin is critical to plant growth and development, as well as stress responses.Small auxin-up RNA(SAUR) is the largest family of early auxin responsive genes in higher plants. However, the function of fewSAURgenes is known owing to functional redundancy among the many family members.ResultsIn this study, we conducted a phylogenetic analysis using protein sequences of 795 SAURs fromAnthoceros angustus,Marchantia polymorpha,Physcomitrella patens,Selaginella moellendorffii,Ginkgo biloba,Gnetum montanum,Amborella trichopoda,Arabidopsis thaliana,Oryza sativa,Zea mays,Glycine max,Medicago truncatulaandSetaria italica. The phylogenetic trees showed that the SAUR proteins could be divided into 10 clades and three subfamilies, and that SAUR proteins of three bryophyte species were only located in subfamily III, which suggested that they may be ancestral. From bryophyta to anthophyta,SAURfamily have appeared very large expansion. The number ofSAURgene in Fabaceae species was considerably higher than that in other plants, which may be associated with independent whole genome duplication event in the Fabaceae lineages. The phylogenetic trees also showed thatSAURgenes had expanded independently monocotyledons and dicotyledons in angiosperms. Conserved motif and protein structure prediction revealed that SAUR proteins were highly conserved among higher plants, and two leucine residues in motif I were observed in almost all SAUR proteins, which suggests the residues plays a critical role in the stability and function of SAUR proteins. Expression analysis ofSAURgenes using publicly available RNA-seq data from rice and soybean indicated functional similarity of members in the same clade, which was also further confirmed by qRT-PCR. Summarization of SAUR functions also showed that SAUR functions were usually consistent within a subclade.ConclusionsThis study provides insights into the evolution and function of theSAURgene family from bryophyta to anthophyta, particularly in Fabaceae plants. Future investigation to understand the functions ofSAURfamily members should employ a clade as the study unit.
Response of phytohormone mediated plant homeodomain (PHD) family to abiotic stress in upland cotton (Gossypium hirsutum spp.)
Authors: Wu Huanhuan , Zheng Lei , Qanmber Ghulam , Guo Mengzhen , Wang Zhi , Yang Zuoren 
Published: January 2021

AbstractBackgroundThe sequencing and annotations of cotton genomes provide powerful theoretical support to unravel more physiological and functional information. Plant homeodomain (PHD) protein family has been reported to be involved in regulating various biological processes in plants. However, their functional studies have not yet been carried out in cotton.ResultsIn this study, 108, 55, and 52PHDgenes were identified inG. hirsutum,G. raimondii, andG. arboreum, respectively. A total of 297PHDgenes from three cotton species,Arabidopsis, and rice were divided into five groups. We performed chromosomal location, phylogenetic relationship, gene structure, and conserved domain analysis forGhPHDgenes.GhPHDgenes were unevenly distributed on each chromosome. However, moreGhPHDgenes were distributed on At_05, Dt_05, and At_07 chromosomes. GhPHD proteins depicted conserved domains, andGhPHDgenes exhibiting similar gene structure were clustered together. Further, whole genome duplication (WGD) analysis indicated that purification selection greatly contributed to the functional maintenance ofGhPHDgene family. Expression pattern analysis based on RNA-seq data showed that mostGhPHDgenes showed clear tissue-specific spatiotemporal expression patterns elucidating the multiple functions ofGhPHDsin plant growth and development. Moreover, analysis ofcis-acting elements revealed thatGhPHDsmay respond to a variety of abiotic and phytohormonal stresses. In this regard, someGhPHDgenes showed good response against abiotic and phytohormonal stresses. Additionally, co-expression network analysis indicated thatGhPHDsare essential for plant growth and development, whileGhPHDgenes response against abiotic and phytohormonal stresses may help to improve plant tolerance in adverse environmental conditions.ConclusionThis study will provide useful information to facilitate further research related to the vital roles ofGhPHDgene family in plant growth and development.