BACKGROUND: G-quadruplexes (G4s), formed within guanine-rich nucleic acids, are secondary structures involved in important biological processes. Although every G4 motif has the potential to form a stable G4 structure, not every G4 motif would, and accurate energy-based methods are needed to assess their structural stability. Here, we present a decision tree-based prediction tool, G4Boost, to identify G4 motifs and predict their secondary structure folding probability and thermodynamic stability based on their sequences, nucleotide compositions, and estimated structural topologies. RESULTS: of 0.95 only by the means of sequence intrinsic feature. G4Boost was successfully applied and validated to predict the stability of experimentally-determined G4 structures, including for plants and humans. CONCLUSION: G4Boost outperformed the three machine-learning based prediction tools, DeepG4, Quadron, and G4RNA Screener, in terms of both accuracy and F1-score, and can be highly useful for G4 prediction to understand gene regulation across species including plants and humans.

BACKGROUND: Gene annotation in eukaryotes is a non-trivial task that requires meticulous analysis of accumulated transcript data. Challenges include transcriptionally active regions of the genome that contain overlapping genes, genes that produce numerous transcripts, transposable elements and numerous diverse sequence repeats. Currently available gene annotation software applications depend on pre-constructed full-length gene sequence assemblies which are not guaranteed to be error-free. The origins of these sequences are often uncertain, making it difficult to identify and rectify errors in them. This hinders the creation of an accurate and holistic representation of the transcriptomic landscape across multiple tissue types and experimental conditions. Therefore, to gauge the extent of diversity in gene structures, a comprehensive analysis of genome-wide expression data is imperative. RESULTS: We present FINDER, a fully automated computational tool that optimizes the entire process of annotating genes and transcript structures. Unlike current state-of-the-art pipelines, FINDER automates the RNA-Seq pre-processing step by working directly with raw sequence reads and optimizes gene prediction from BRAKER2 by supplementing these reads with associated proteins. The FINDER pipeline (1) reports transcripts and recognizes genes that are expressed under specific conditions, (2) generates all possible alternatively spliced transcripts from expressed RNA-Seq data, (3) analyzes read coverage patterns to modify existing transcript models and create new ones, and (4) scores genes as high- or low-confidence based on the available evidence across multiple datasets. We demonstrate the ability of FINDER to automatically annotate a diverse pool of genomes from eight species. CONCLUSIONS: FINDER takes a completely automated approach to annotate genes directly from raw expression data. It is capable of processing eukaryotic genomes of all sizes and requires no manual supervision-ideal for bench researchers with limited experience in handling computational tools.

We describe JBrowse Connect, an optional expansion to the JBrowse genome browser, targeted at developers. JBrowse Connect allows live messaging, notifications for new annotation tracks, heavy-duty analyses initiated by the user from within the browser, and other dynamic features. We present example applications of JBrowse Connect that allow users 1) to specify and execute BLAST searches by either running on the same host as the webserver, with a self-contained BLAST module leveraging NCBI Blast+ commands, or via a managed Galaxy instance that can optionally run on a different host, and 2) to run the primer design service Primer3. JBrowse Connect allows users to track job progress and view results in the context of the browser. The software is available under a choice of open source licenses including LGPL and the Artistic License.

MOTIVATION: Plant breeding aims to improve current germplasm that can tolerate a wide range of biotic and abiotic stresses. To accomplish this goal, breeders rely on developing a deeper understanding of genetic makeup and relationships between plant varieties to make informed plant selections. Although rapid advances in genotyping technology generated a large amount of data for breeders, tools that facilitate pedigree analysis and visualization are scant, leaving breeders to use classical, but inherently limited, hierarchical pedigree diagrams for a handful of plant varieties. To answer this need, we developed a simple web-based tool that can be easily implemented at biological databases, called PedigreeNet, to create and visualize customizable pedigree relationships in a network context, displaying pre- and user-uploaded data. RESULTS: As a proof-of-concept, we implemented PedigreeNet at the maize model organism database, MaizeGDB. The PedigreeNet viewer at MaizeGDB has a dynamically-generated pedigree network of 4706 maize lines and 5487 relationships that are currently available as both a stand-alone web-based tool and integrated directly on the MaizeGDB Stock Pages. The tool allows the user to apply a number of filters, select or upload their own breeding relationships, center a pedigree network on a plant variety, identify the common ancestor between two varieties, and display the shortest path(s) between two varieties on the pedigree network. The PedigreeNet code layer is written as a JavaScript wrapper around Cytoscape Web. PedigreeNet fills a great need for breeders to have access to an online tool to represent and visually customize pedigree relationships. AVAILABILITY AND IMPLEMENTATION: PedigreeNet is accessible at https://www.maizegdb.org/breeders_toolbox. The open source code is publically and freely available at GitHub: https://github.com/Maize-Genetics-and-Genomics-Database/PedigreeNet. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

SUMMARY: Methods to automatically integrate sequence information with physical and genetic maps are scarce. The Locus Lookup tool enables researchers to define windows of genomic sequence likely to contain loci of interest where only genetic or physical mapping associations are reported. Using the Locus Lookup tool, researchers will be able to locate specific genes more efficiently that will ultimately help them develop a better maize plant. With the availability of the well-documented source code, the tool can be easily adapted to other biological systems. AVAILABILITY: The Locus Lookup tool is available on the web at http://maizegdb.org/cgi-bin/locus_lookup.cgi. It is implemented in PHP, Oracle and Apache, with all major browsers supported. Source code is freely available for download at http://ftp.maizegdb.org/open_source/locus_lookup/.

One of the challenges in protein secondary structure prediction is to overcome the cross-validated 80% prediction accuracy barrier. Here, we propose a novel approach to surpass this barrier. Instead of using a single algorithm that relies on a limited data set for training, we combine two complementary methods having different strengths: Fragment Database Mining (FDM) and GOR V. FDM harnesses the availability of the known protein structures in the Protein Data Bank and provides highly accurate secondary structure predictions when sequentially similar structural fragments are identified. In contrast, the GOR V algorithm is based on information theory, Bayesian statistics, and PSI-BLAST multiple sequence alignments to predict the secondary structure of residues inside a sliding window along a protein chain. A combination of these two different methods benefits from the large number of structures in the PDB and significantly improves the secondary structure prediction accuracy, resulting in Q3 ranging from 67.5 to 93.2%, depending on the availability of highly similar fragments in the Protein Data Bank.

BACKGROUND: The abundant data available for protein interaction networks have not yet been fully understood. New types of analyses are needed to reveal organizational principles of these networks to investigate the details of functional and regulatory clusters of proteins. RESULTS: In the present work, individual clusters identified by an eigenmode analysis of the connectivity matrix of the protein-protein interaction network in yeast are investigated for possible functional relationships among the members of the cluster. With our functional clustering we have successfully predicted several new protein-protein interactions that indeed have been reported recently. CONCLUSION: Eigenmode analysis of the entire connectivity matrix yields both a global and a detailed view of the network. We have shown that the eigenmode clustering not only is guided by the number of proteins with which each protein interacts, but also leads to functional clustering that can be applied to predict new protein interactions.

Summary: We have created the GOR V web server for protein secondary structure prediction. The GOR V algorithm combines information theory, Bayesian statistics and evolutionary information. In its fifth version, the GOR method reached (with the full jack-knife procedure) an accuracy of prediction Q3 of 73.5%. Although GOR V has been among the most successful methods, its online unavailability has been a deterrent to its popularity. Here, we remedy this situation by creating the GOR V server. Availability: The GOR V server is freely accessible to public users and private institutions at http://gor.bb.iastate.edu/ Contact: [email protected]

BACKGROUND: Protein-protein interactions play a critical role in protein function. Completion of many genomes is being followed rapidly by major efforts to identify interacting protein pairs experimentally in order to decipher the networks of interacting, coordinated-in-action proteins. Identification of protein-protein interaction sites and detection of specific amino acids that contribute to the specificity and the strength of protein interactions is an important problem with broad applications ranging from rational drug design to the analysis of metabolic and signal transduction networks. RESULTS: In order to increase the power of predictive methods for protein-protein interaction sites, we have developed a consensus methodology for combining four different methods. These approaches include: data mining using Support Vector Machines, threading through protein structures, prediction of conserved residues on the protein surface by analysis of phylogenetic trees, and the Conservatism of Conservatism method of Mirny and Shakhnovich. Results obtained on a dataset of hydrolase-inhibitor complexes demonstrate that the combination of all four methods yield improved predictions over the individual methods. CONCLUSIONS: We developed a consensus method for predicting protein-protein interface residues by combining sequence and structure-based methods. The success of our consensus approach suggests that similar methodologies can be developed to improve prediction accuracies for other bioinformatic problems.