Search

Motivation Figures in biomedical papers communicate essential information with the potential to identify relevant documents in biomedical and clinical settings. However, academic search interfaces mainly search over text fields. Results We describe a search system for biomedical documents that leverages image modalities and an existing index server. We integrate a problem-specific taxonomy of image modalities and image-based data into a custom search system. Our solution features a front-end interface to enhance classical document search results with image-related data, including page thumbnails, figures, captions and image-modality information. We demonstrate the system on a subset of the CORD-19 document collection. A quantitative evaluation demonstrates higher precision and recall for biomedical document retrieval. A qualitative evaluation with domain experts further highlights our solution's benefits to biomedical search. Availability and implementation A demonstration is available at https://runachay.evl.uic.edu/scholar. Our code and image models can be accessed via github.com/uic-evl/bio-search. The dataset is continuously expanded. [ABSTRACT FROM AUTHOR]

Motivation We explore the use of literature-curated signed causal gene expression and gene–function relationships to construct unsupervised embeddings of genes, biological functions and diseases. Our goal is to prioritize and predict activating and inhibiting functional associations of genes and to discover hidden relationships between functions. As an application, we are particularly interested in the automatic construction of networks that capture relevant biology in a given disease context. Results We evaluated several unsupervised gene embedding models leveraging literature-curated signed causal gene expression findings. Using linear regression, we show that, based on these gene embeddings, gene–function relationships can be predicted with about 95% precision for the highest scoring genes. Function embedding vectors, derived from parameters of the linear regression model, allow inference of relationships between different functions or diseases. We show for several diseases that gene and function embeddings can be used to recover key drivers of pathogenesis, as well as underlying cellular and physiological processes. These results are presented as disease-centric networks of genes and functions. To illustrate the applicability of our approach to other machine learning tasks, we also computed embeddings for drug molecules, which were then tested using a simple neural network to predict drug–disease associations. Availability and implementation Python implementations of the gene and function embedding algorithms operating on a subset of our literature-curated content as well as other code used for this paper are made available as part of the Supplementary data. Supplementary information Supplementary data are available at Bioinformatics Advances online. [ABSTRACT FROM AUTHOR]

Motivation Development of bioinformatics methods is a long, complex and resource-hungry process. Hundreds of these tools were released. While some methods are highly cited and used, many suffer relatively low citation rates. We empirically analyze a large collection of recently released methods in three diverse protein function and disorder prediction areas to identify key factors that contribute to increased citations. Results We show that provision of a working web server significantly boosts citation rates. On average, methods with working web servers generate three times as many citations compared to tools that are available as only source code, have no code and no server, or are no longer available. This observation holds consistently across different research areas and publication years. We also find that differences in predictive performance are unlikely to impact citation rates. Overall, our empirical results suggest that a relatively low-cost investment into the provision and long-term support of web servers would substantially increase the impact of bioinformatics tools. [ABSTRACT FROM AUTHOR]

Summary ExRec (Exclusion of Recombined DNA) is a dependency-free Python pipeline that implements the four-gamete test to automatically filter out recombined DNA blocks from thousands of DNA sequence loci. This procedure helps all loci better meet the "no intralocus recombination" assumption common to many coalescent-based analyses in population genomic, phylogeographic, and shallow-scale phylogenomic studies. The user-friendly pipeline contains five standalone applications—four file conversion scripts and one main script that performs the recombination filtering procedures. The pipeline outputs recombination-filtered data in a variety of common formats and a tab-delimited table that displays descriptive statistics for all loci and the analysis results. A novel feature of this software is that the user can select whether to output the longest nonrecombined sequence blocks from recombined loci (current best practice) or randomly select nonrecombined blocks from loci (a newer approach). We tested ExRec with six published phylogenomic datasets that ranged in size from 27 to 2237 loci and came in a variety of input file formats. In all trials the data could be easily analyzed in only seconds for the smaller datasets and <30 min for the largest using a simple laptop computer. Availability and implementation ExRec was written in Python 3 under the MIT license. The program applications, user manual (including step-by-step tutorials), and sample data are freely available at https://github.com/Sammccarthypotter/ExRec. [ABSTRACT FROM AUTHOR]

Summary PICAFlow is a R-written integrative workflow dedicated to flow/mass cytometry data handling, from pre-processing to deep and comprehensive analysis. It is designed as a powerful all-in-one tool which contains all the necessary functions and packages presented in a user-friendly and ease-to-use fashion. PICAFlow also includes important features that are very frequently lacking in other close software, such as interactive R Shiny applications for real-time data transformation and compensation as well as normalization methods aiming to remove batch effects and unwanted inter- and intra-group heterogeneity. It also allows to perform dimensionality reduction, cell clustering (using different available approaches), as well as complementary statistical analyses and export different support for data interpretation and visualization. Availability PICAFlow is available as a R-written package hosted at the following GitHub repository: https://github.com/PaulRegnier/PICAFlow and is complemented by a fully detailed tutorial available at the following URL: https://paul-regnier.fr/tutoriel-picaflow/. [ABSTRACT FROM AUTHOR]

Motivation Biologists increasingly turn to machine learning models not just to predict, but to explain. Feature reduction is a common approach to improve both the performance and interpretability of models. However, some biological datasets, such as microbiome data, are inherently organized in a taxonomy, but these hierarchical relationships are not leveraged during feature reduction. We sought to design a feature engineering algorithm to exploit relationships in hierarchically organized biological data. Results We designed an algorithm, called TaxaHFE, to collapse information-poor features into their higher taxonomic levels. We applied TaxaHFE to six previously published datasets and found, on average, a 90% reduction in the number of features (SD = 5.1%) compared to using the most complete taxonomy. Using machine learning to compare the most resolved taxonomic level (i.e. species) against TaxaHFE-preprocessed features, models based on TaxaHFE features achieved an average increase of 3.47% in receiver operator curve area under the curve. Compared to other hierarchical feature engineering implementations, TaxaHFE introduces the novel ability to consider both categorical and continuous response variables to inform the feature set collapse. Importantly, we find TaxaHFE's ability to reduce hierarchically organized features to a more information-rich subset increases the interpretability of models. Availability and implementation TaxaHFE is available as a Docker image and as R code at https://github.com/aoliver44/taxaHFE. [ABSTRACT FROM AUTHOR]

Motivation K -mer hashing is a common operation in many foundational bioinformatics problems. However, generic string hashing algorithms are not optimized for this application. Strings in bioinformatics use specific alphabets, a trait leveraged for nucleic acid sequences in earlier work. We note that amino acid sequences, with complexities and context that cannot be captured by generic hashing algorithms, can also benefit from a domain-specific hashing algorithm. Such a hashing algorithm can accelerate and improve the sensitivity of bioinformatics applications developed for protein sequences. Results Here, we present aaHash, a recursive hashing algorithm tailored for amino acid sequences. This algorithm utilizes multiple hash levels to represent biochemical similarities between amino acids. aaHash performs ∼10× faster than generic string hashing algorithms in hashing adjacent k -mers. Availability and implementation aaHash is available online at https://github.com/bcgsc/btllib and is free for academic use. [ABSTRACT FROM AUTHOR]

Motivation The fast and accurate detection of similar geometrical arrangements of protein residues, known as 3D structural motifs, is highly relevant for many applications such as binding region and catalytic site detection, drug discovery and structure conservation analyses. With the recent publication of new protein structure prediction methods, the number of available protein structures is exploding, which makes efficient and easy-to-use tools for identifying 3D structural motifs essential. Results We present an open-source Python package that enables the search for both exact and mutated motifs with position-specific residue substitutions. The tool is efficient, flexible, accurate, and suitable to run both on computer clusters and personal laptops. Two successful applications of pyScoMotif for catalytic site identification are showcased. Availability and implementation The pyScoMotif package can be installed from the PyPI repository and is also available at https://github.com/3BioCompBio/pyScoMotif. It is free to use for non-commercial purposes. [ABSTRACT FROM AUTHOR]

Motivation Higher-order interaction patterns among proteins have the potential to reveal mechanisms behind molecular processes and diseases. While clustering methods are used to identify functional groups within molecular interaction networks, these methods largely focus on edge density and do not explicitly take into consideration higher-order interactions. Disease genes in these networks have been shown to exhibit rich higher-order structure in their vicinity, and considering these higher-order interaction patterns in network clustering have the potential to reveal new disease-associated modules. Results We propose a higher-order community detection method which identifies community structure in networks with respect to specific higher-order connectivity patterns beyond edges. Higher-order community detection on four different protein–protein interaction networks identifies biologically significant modules and disease modules that conventional edge-based clustering methods fail to discover. Higher-order clusters also identify disease modules from genome-wide association study data, including new modules that were not discovered by top-performing approaches in a Disease Module DREAM Challenge. Our approach provides a more comprehensive view of community structure that enables us to predict new disease–gene associations. Availability and implementation https://github.com/Reed-CompBio/graphlet-clustering. [ABSTRACT FROM AUTHOR]

Motivation Positive-unlabeled data consists of points with either positive or unknown labels. It is widespread in medical, genetic, and biological settings, creating a high demand for predictive positive-unlabeled models. The performance of such models is usually estimated using validation sets, assumed to be selected completely at random (SCAR) from known positive examples. For certain metrics, this assumption enables unbiased performance estimation when treating positive-unlabeled data as positive/negative. However, the SCAR assumption is often adopted without proper justifications, simply for the sake of convenience. Results We provide an algorithm that under the weak assumptions of a lower bound on the number of positive examples can test for the violation of the SCAR assumption. Applying it to the problem of gene prioritization for complex genetic traits, we illustrate that the SCAR assumption is often violated there, causing the inflation of performance estimates, which we refer to as validation bias. We estimate the potential impact of validation bias on performance estimation. Our analysis reveals that validation bias is widespread in gene prioritization data and can significantly overestimate the performance of models. This finding elucidates the discrepancy between the reported good performance of models and their limited practical applications. Availability and implementation Python code with examples of application of the validation bias detection algorithm is available at github.com/ArtomovLab/ValidationBias. [ABSTRACT FROM AUTHOR]

Summary We present bubbleHeatmap, an R plotting package which combines elements of a bubble plot and heatmap to conveniently display two numerical variables for each data point across a categorical two dimensional grid. This has particular advantages for visualizing the 251 metabolomic measures produced by the automated, high-throughput, 1H-NMR-based platform provided by Nightingale Health, which includes 12 measures repeated across each of 14 lipoprotein subclasses. As these metabolomic profiles are currently available for large biobanks, we provide a figure template to aid the use of bubbleHeatmap in displaying results from analyses using these data. Availability and implementation https://cran.r-project.org/web/packages/bubbleHeatmap [ABSTRACT FROM AUTHOR]

Motivation Most sequence alignment techniques make use of exact k -mer hits, called seeds, as anchors to optimize alignment speed. A large number of bioinformatics tools employing seed-based alignment techniques, such as Minimap2 ⁠ , use a single value of k per sequencing technology, without a strong guarantee that this is the best possible value. Given the ubiquity of sequence alignment, identifying values of k that lead to more sensitive alignments is thus an important task. To aid this, we present Seedability ⁠ , a seed-based alignment framework designed for estimating an optimal seed k -mer length (as well as a minimal number of shared seeds) based on a given alignment identity threshold. In particular, we were motivated to make Minimap2 more sensitive in the pairwise alignment of short sequences. Results The experimental results herein show improved alignments of short and divergent sequences when using the parameter values determined by Seedability in comparison to the default values of Minimap2 ⁠. We also show several cases of pairs of real divergent sequences, where the default parameter values of Minimap2 yield no output alignments, but the values output by Seedability produce plausible alignments. Availability and implementation https://github.com/lorrainea/Seedability (distributed under GPL v3.0). [ABSTRACT FROM AUTHOR]

Motivation The accuracy gap between predicted and experimental structures has been significantly reduced following the development of AlphaFold2 (AF2). However, for many targets, AF2 models still have room for improvement. In previous CASP experiments, highly computationally intensive MD simulation-based methods have been widely used to improve the accuracy of single 3D models. Here, our ReFOLD pipeline was adapted to refine AF2 predictions while maintaining high model accuracy at a modest computational cost. Furthermore, the AF2 recycling process was utilized to improve 3D models by using them as custom template inputs for tertiary and quaternary structure predictions. Results According to the Molprobity score, 94% of the generated 3D models by ReFOLD were improved. AF2 recycling showed an improvement rate of 87.5% (using MSAs) and 81.25% (using single sequences) for monomeric AF2 models and 100% (MSA) and 97.8% (single sequence) for monomeric non-AF2 models, as measured by the average change in lDDT. By the same measure, the recycling of multimeric models showed an improvement rate of as much as 80% for AF2-Multimer (AF2M) models and 94% for non-AF2M models. Availability and implementation Refinement using AlphaFold2-Multimer recycling is available as part of the MultiFOLD docker package (https://hub.docker.com/r/mcguffin/multifold). The ReFOLD server is available at https://www.reading.ac.uk/bioinf/ReFOLD/ and the modified scripts can be downloaded from https://www.reading.ac.uk/bioinf/downloads/. Supplementary information Supplementary data are available at Bioinformatics Advances online. [ABSTRACT FROM AUTHOR]

Summary The positional Burrows–Wheeler transform (PBWT) data structure allows for efficient haplotype data matching and compression. Its performance makes it a powerful tool for bioinformatics. However, existing algorithms do not exploit parallelism due to inner dependencies. We introduce a new method to break the dependencies and show how to fully exploit modern multi-core processors. Availability and implementation Source code and applications are available at https://github.com/rwk-unil/parallel%5fpbwt. Supplementary information Supplementary data are available at Bioinformatics Advances online. [ABSTRACT FROM AUTHOR]

Summary Multiple sequence alignment is a basic part of many bioinformatics pipelines, including in phylogeny estimation, prediction of structure for both RNAs and proteins, and metagenomic sequence analysis. Yet many sequence datasets exhibit substantial sequence length heterogeneity, both because of large insertions and deletions in the evolutionary history of the sequences and the inclusion of unassembled reads or incompletely assembled sequences in the input. A few methods have been developed that can be highly accurate in aligning datasets with sequence length heterogeneity, with UPP one of the first methods to achieve good accuracy, and WITCH a recent improvement on UPP for accuracy. In this article, we show how we can speed up WITCH. Our improvement includes replacing a critical step in WITCH (currently performed using a heuristic search) by a polynomial time exact algorithm using Smith–Waterman. Our new method, WITCH-NG (i.e. 'next generation WITCH') achieves the same accuracy but is substantially faster. WITCH-NG is available at https://github.com/RuneBlaze/WITCH-NG. Availability and implementation The datasets used in this study are from prior publications and are freely available in public repositories, as indicated in the Supplementary Materials. Supplementary information Supplementary data are available at Bioinformatics Advances online. [ABSTRACT FROM AUTHOR]

Summary The transformer-based language models, including vanilla transformer, BERT and GPT-3, have achieved revolutionary breakthroughs in the field of natural language processing (NLP). Since there are inherent similarities between various biological sequences and natural languages, the remarkable interpretability and adaptability of these models have prompted a new wave of their application in bioinformatics research. To provide a timely and comprehensive review, we introduce key developments of transformer-based language models by describing the detailed structure of transformers and summarize their contribution to a wide range of bioinformatics research from basic sequence analysis to drug discovery. While transformer-based applications in bioinformatics are diverse and multifaceted, we identify and discuss the common challenges, including heterogeneity of training data, computational expense and model interpretability, and opportunities in the context of bioinformatics research. We hope that the broader community of NLP researchers, bioinformaticians and biologists will be brought together to foster future research and development in transformer-based language models, and inspire novel bioinformatics applications that are unattainable by traditional methods. Supplementary information Supplementary data are available at Bioinformatics Advances online. [ABSTRACT FROM AUTHOR]

Motivation RNA consensus secondary structure prediction from aligned sequences is a powerful approach for improving the secondary structure prediction accuracy. However, because the computational complexities of conventional prediction tools scale with the cube of the alignment lengths, their application to long RNA sequences, such as viral RNAs or long non-coding RNAs, requires significant computational time. Results In this study, we developed LinAliFold and CentroidLinAliFold, fast RNA consensus secondary structure prediction tools based on minimum free energy and maximum expected accuracy principles, respectively. We achieved software acceleration using beam search methods that were successfully used for fast secondary structure prediction from a single RNA sequence. Benchmark analyses showed that LinAliFold and CentroidLinAliFold were much faster than the existing methods while preserving the prediction accuracy. As an empirical application, we predicted the consensus secondary structure of coronaviruses with approximately 30 000 nt in 5 and 79 min by LinAliFold and CentroidLinAliFold, respectively. We confirmed that the predicted consensus secondary structure of coronaviruses was consistent with the experimental results. Availability and implementation The source codes of LinAliFold and CentroidLinAliFold are freely available at https://github.com/fukunagatsu/LinAliFold-CentroidLinAliFold. Supplementary information Supplementary data are available at Bioinformatics Advances online. [ABSTRACT FROM AUTHOR]

Motivation Data normalization is essential to ensure accurate inference and comparability of gene expression measures across samples or conditions. Ideally, gene expression data should be rescaled based on consistently expressed reference genes. However, to normalize biologically diverse samples, the most commonly used reference genes exhibit striking expression variability and size-factor or distribution-based normalization methods can be problematic when the amount of asymmetry in differential expression is significant. Results We report an efficient and accurate data-driven method—Cosine score-based iterative normalization (Cosbin)—to normalize biologically diverse samples. Based on the Cosine scores of cross-condition expression patterns, the Cosbin pipeline iteratively eliminates asymmetric differentially expressed genes, identifies consistently expressed genes, and calculates sample-wise normalization factors. We demonstrate the superior performance and enhanced utility of Cosbin compared with six representative peer methods using both simulation and real multi-omics expression datasets. Implemented in open-source R scripts and specifically designed to address normalization bias due to significant asymmetry in differential expression across multiple conditions, the Cosbin tool complements rather than replaces the existing methods and will allow biologists to more accurately detect true molecular signals among diverse phenotypic groups. Availability and implementation The R scripts of Cosbin pipeline are freely available at https://github.com/MinjieSh/Cosbin. Supplementary information Supplementary data are available at Bioinformatics Advances online. [ABSTRACT FROM AUTHOR]

Motivation Recently introduced, linked-read technologies, such as the 10× chromium system, use microfluidics to tag multiple short reads from the same long fragment (50–200 kb) with a small sequence, called a barcode. They are inexpensive and easy to prepare, combining the accuracy of short-read sequencing with the long-range information of barcodes. The same barcode can be used for several different fragments, which complicates the analyses. Results We present QuickDeconvolution (QD), a new software for deconvolving a set of reads sharing a barcode, i.e. separating the reads from the different fragments. QD only takes sequencing data as input, without the need for a reference genome. We show that QD outperforms existing software in terms of accuracy, speed and scalability, making it capable of deconvolving previously inaccessible data sets. In particular, we demonstrate here the first example in the literature of a successfully deconvoluted animal sequencing dataset, a 33-Gb Drosophila melanogaster dataset. We show that the taxonomic assignment of linked reads can be improved by deconvoluting reads with QD before taxonomic classification. Availability and implementation Code and instructions are available on https://github.com/RolandFaure/QuickDeconvolution. Supplementary information Supplementary data are available at Bioinformatics Advances online. [ABSTRACT FROM AUTHOR]

Motivation Methods for the global measurement of transcript abundance such as microarrays and RNA-Seq generate datasets in which the number of measured features far exceeds the number of observations. Extracting biologically meaningful and experimentally tractable insights from such data therefore requires high-dimensional prediction. Existing sparse linear approaches to this challenge have been stunningly successful, but some important issues remain. These methods can fail to select the correct features, predict poorly relative to non-sparse alternatives or ignore any unknown grouping structures for the features. Results We propose a method called SuffPCR that yields improved predictions in high-dimensional tasks including regression and classification, especially in the typical context of omics with correlated features. SuffPCR first estimates sparse principal components and then estimates a linear model on the recovered subspace. Because the estimated subspace is sparse in the features, the resulting predictions will depend on only a small subset of genes. SuffPCR works well on a variety of simulated and experimental transcriptomic data, performing nearly optimally when the model assumptions are satisfied. We also demonstrate near-optimal theoretical guarantees. Availability and implementation Code and raw data are freely available at https://github.com/dajmcdon/suffpcr. Package documentation may be viewed at https://dajmcdon.github.io/suffpcr. Contact daniel@stat.ubc.ca Supplementary information Supplementary data are available at Bioinformatics Advances online. [ABSTRACT FROM AUTHOR]

Motivation Federated learning enables privacy-preserving machine learning in the medical domain because the sensitive patient data remain with the owner and only parameters are exchanged between the data holders. The federated scenario introduces specific challenges related to the decentralized nature of the data, such as batch effects and differences in study population between the sites. Here, we investigate the challenges of moving classical analysis methods to the federated domain, specifically principal component analysis (PCA), a versatile and widely used tool, often serving as an initial step in machine learning and visualization workflows. We provide implementations of different federated PCA algorithms and evaluate them regarding their accuracy for high-dimensional biological data using realistic sample distributions over multiple data sites, and their ability to preserve downstream analyses. Results Federated subspace iteration converges to the centralized solution even for unfavorable data distributions, while approximate methods introduce error. Larger sample sizes at the study sites lead to better accuracy of the approximate methods. Approximate methods may be sufficient for coarse data visualization, but are vulnerable to outliers and batch effects. Before the analysis, the PCA algorithm, as well as the number of eigenvectors should be considered carefully to avoid unnecessary communication overhead. Availability and implementation Simulation code and notebooks for federated PCA can be found at https://gitlab.com/roettgerlab/federatedPCA ; the code for the federated app is available at https://github.com/AnneHartebrodt/fc-federated-pca Supplementary information Supplementary data are available at Bioinformatics Advances online. [ABSTRACT FROM AUTHOR]

Motivation The accumulation of sequencing data has enabled researchers to predict the interactions between RNA sequences and RNA-binding proteins (RBPs) using novel machine learning techniques. However, existing models are often difficult to interpret and require additional information to sequences. Bidirectional encoder representations from transformer (BERT) is a language-based deep learning model that is highly interpretable. Therefore, a model based on BERT architecture can potentially overcome such limitations. Results Here, we propose BERT-RBP as a model to predict RNA–RBP interactions by adapting the BERT architecture pretrained on a human reference genome. Our model outperformed state-of-the-art prediction models using the eCLIP-seq data of 154 RBPs. The detailed analysis further revealed that BERT-RBP could recognize both the transcript region type and RNA secondary structure only based on sequence information. Overall, the results provide insights into the fine-tuning mechanism of BERT in biological contexts and provide evidence of the applicability of the model to other RNA-related problems. Availability and implementation Python source codes are freely available at https://github.com/kkyamada/bert-rbp. The datasets underlying this article were derived from sources in the public domain: [RBPsuite (http://www.csbio.sjtu.edu.cn/bioinf/RBPsuite/), Ensembl Biomart (http://asia.ensembl.org/biomart/martview/)]. Supplementary information Supplementary data are available at Bioinformatics Advances online. [ABSTRACT FROM AUTHOR]

Motivation Cell-type abundance data arising from mass cytometry experiments are compositional in nature. Classical association tests do not apply to the compositional data due to their non-Euclidean nature. Existing methods for analysis of cell type abundance data suffer from several limitations for high-dimensional mass cytometry data, especially when the sample size is small. Results We proposed a new multivariate statistical learning methodology, Compositional Data Analysis using Kernels (CODAK), based on the kernel distance covariance (KDC) framework to test the association of the cell type compositions with important predictors (categorical or continuous) such as disease status. CODAK scales well for high-dimensional data and provides satisfactory performance for small sample sizes (n  < 25). We conducted simulation studies to compare the performance of the method with existing methods of analyzing cell type abundance data from mass cytometry studies. The method is also applied to a high-dimensional dataset containing different subgroups of populations including Systemic Lupus Erythematosus (SLE) patients and healthy control subjects. Availability and implementation CODAK is implemented using R. The codes and the data used in this manuscript are available on the web at http://github.com/GhoshLab/CODAK/. Contact prudra@okstate.edu Supplementary information Supplementary data are available at Bioinformatics Advances online. [ABSTRACT FROM AUTHOR]

Motivation Alternative splicing is a ubiquitous process in eukaryotes that allows distinct transcripts to be produced from the same gene. Yet, the study of transcript evolution within a gene family is still in its infancy. One prerequisite for this study is the availability of methods to compare sets of transcripts while accounting for their splicing structure. In this context, we generalize the concept of pairwise spliced alignments (PSpAs) to multiple spliced alignments (MSpAs). MSpAs have several important purposes in addition to empowering the study of the evolution of transcripts. For instance, it is a key to improving the prediction of gene models, which is important to solve the growing problem of genome annotation. Despite its essentialness, a formal definition of the concept and methods to compute MSpAs are still lacking. Results We introduce the MSpA problem and the SplicedFamAlignMulti (SFAM) method, to compute the MSpA of a gene family. Like most multiple sequence alignment (MSA) methods that are generally greedy heuristic methods assembling pairwise alignments, SFAM combines all PSpAs of coding DNA sequences and gene sequences of a gene family into an MSpA. It produces a single structure that represents the superstructure and models of the gene family. Using real vertebrate and simulated gene family data, we illustrate the utility of SFAM for computing accurate gene family superstructures, MSAs, inferring splicing orthologous groups and improving gene-model annotations. Availability and implementation The supporting data and implementation of SFAM are freely available at https://github.com/UdeS-CoBIUS/SpliceFamAlignMulti. Supplementary information Supplementary data are available at Bioinformatics Advances online. [ABSTRACT FROM AUTHOR]

Motivation The release of AlphaFold 2.0 has revolutionized our ability to determine protein structures from sequences. This tool also inadvertently opens up many unanticipated opportunities. In this article, we investigate the AntiFam resource, which contains 250 protein sequence families that we believe to be spurious protein translations. We would not expect proteins belonging to these families to fold into well-ordered globular structures. To test this hypothesis, we have attempted to computationally determine the structure of a representative sequence from all AntiFam 6.0 families. Results Although the large majority of families showed no evidence of globular structure, we have identified one example for which a globular structure is predicted. Proteins in this AntiFam entry indeed seem likely to be bona fide proteins, based on additional considerations, and thus AlphaFold provides a useful quality control for the AntiFam database. Conversely, known spurious proteins offer useful set of quality controls for AlphaFold. We have identified a trend that the mean structure prediction confidence score pLDDT is higher for shorter sequences. Of the 131 AntiFam representative sequences <100 amino acids in length, AlphaFold predicts a mean pLDDT of 80 or greater for six of them. Thus, particular care should be taken when applying AlphaFold to short protein sequences. Availability and implementation The AlphaFold predictions for representative sequences can be found at the following URL: https://drive.google.com/drive/folders/1u9OocRIAabGQn56GljoG1JTDAxjkY1ro. Supplementary information Supplementary data are available at Bioinformatics Advances online. [ABSTRACT FROM AUTHOR]

Motivation Leveraging cross-species information in protein function prediction can add significant power to network-based protein function prediction methods, because so much functional information is conserved across at least close scales of evolution. We introduce MUNDO, a new cross-species co-embedding method that combines a single-network embedding method with a co-embedding method to predict functional annotations in a target species, leveraging also functional annotations in a model species network. Results Across a wide range of parameter choices, MUNDO performs best at predicting annotations in the mouse network, when trained on mouse and human protein–protein interaction (PPI) networks, in the human network, when trained on human and mouse PPIs, and in Baker's yeast, when trained on Fission and Baker's yeast, as compared to competitor methods. MUNDO also outperforms all the cross-species methods when predicting in Fission yeast when trained on Fission and Baker's yeast; however, in this single case, discarding the information from the other species and using annotations from the Fission yeast network alone usually performs best. Availability and implementation All code is available and can be accessed here: github.com/v0rtex20k/MUNDO. Supplementary information Supplementary data are available at Bioinformatics Advances online. Additional experimental results are on our github site. [ABSTRACT FROM AUTHOR]

Motivation: Biological sequence classification is the most fundamental task in bioinformatics analysis. For example, in metagenome analysis, binning is a typical type of DNA sequence classification. In order to classify sequences, it is necessary to define sequence features. The k-mer frequency, base composition and alignment-based metrics are commonly used. On the other hand, in the field of image recognition using machine learning, image classification is broadly divided into those based on shape and those based on style. A style matrix was introduced as a method of expressing the style of an image (e.g. color usage and texture). Results: We propose a novel sequence feature, called genomic style, inspired by image classification approaches, for classifying and clustering DNA sequences. As with the style of images, the DNA sequence is considered to have a genomic style unique to the bacterial species, and the style matrix concept is applied to the DNA sequence. Our main aim is to introduce the genomics style as yet another basic sequence feature for metagenome binning problem in replace of the most commonly used sequence feature k-mer frequency. Performance evaluations showed that our method using a style matrix has the potential for accurate binning when compared with state-of-the-art binning tools based on k-mer frequency. [ABSTRACT FROM AUTHOR]

Motivation: Many bioinformatics resources are provided as ‘web services’, with large databases and analysis software stored on a central server, and clients interacting with them using the hypertext transport protocol (HTTP). While some provide only a visual HTML interface, requiring a web browser to use them, many provide programmatic access using a web application programming interface (API) which returns XML, JSON or plain text that computer programs can interpret more easily. This allows access to be automated. Initially, many bioinformatics APIs used the ‘simple object access protocol’ (SOAP) and, more recently, representational state transfer (REST). Results: GraphQL is a novel, increasingly prevalent alternative to REST and SOAP that represents the available data in the form of a graph to which any conceivable query can be submitted, and which is seeing increasing adoption in industry. Here, we review the principles of GraphQL, outline its particular suitability to the delivery of bioinformatics resources and describe its implementation in our ZincBind resource. [ABSTRACT FROM AUTHOR]