Expansion of the BioCyc collection of pathway/genome databases to 160 genomes

The BioCyc database collection is a set of 160 pathway/genome databases (PGDBs) for most eukaryotic and prokaryotic species whose genomes have been completely sequenced to date. Each PGDB in the BioCyc collection describes the genome and predicted metabolic network of a single organism, inferred from the MetaCyc database, which is a reference source on metabolic pathways from multiple organisms. In addition, each bacterial PGDB includes predicted operons for the corresponding species. The BioCyc collection provides a unique resource for computational systems biology, namely global and comparative analyses of genomes and metabolic networks, and a supplement to the BioCyc resource of curated PGDBs. The Omics viewer available through the BioCyc website allows scientists to visualize combinations of gene expression, proteomics and metabolomics data on the metabolic maps of these organisms. This paper discusses the computational methodology by which the BioCyc collection has been expanded, and presents an aggregate analysis of the collection that includes the range of number of pathways present in these organisms, and the most frequently observed pathways. We seek scientists to adopt and curate individual PGDBs within the BioCyc collection. Only by harnessing the expertise of many scientists we can hope to produce biological databases, which accurately reflect the depth and breadth of knowledge that the biomedical research community is producing

CORRIE: enzyme sequence annotation with confidence estimates

Using a previously developed automated method for enzyme annotation, we report the re-annotation of the ENZYME database and the analysis of local error rates per class. In control experiments, we demonstrate that the method is able to correctly re-annotate 91% of all Enzyme Classification (EC) classes with high coverage (755 out of 827). Only 44 enzyme classes are found to contain false positives, while the remaining 28 enzyme classes are not represented. We also show cases where the re-annotation procedure results in partial overlaps for those few enzyme classes where a certain inconsistency might appear between homologous proteins, mostly due to function specificity. Our results allow the interactive exploration of the EC hierarchy for known enzyme families as well as putative enzyme sequences that may need to be classified within the EC hierarchy. These aspects of our framework have been incorporated into a web-server, called CORRIE, which stands for Correspondence Indicator Estimation and allows the interactive prediction of a functional class for putative enzymes from sequence alone, supported by probabilistic measures in the context of the pre-calculated Correspondence Indicators of known enzymes with the functional classes of the EC hierarchy. The CORRIE server is available at:

Simple ensemble methods are competitive with state-of-the-art data integration methods for gene function prediction

Several works showed that biomolecular data integration is a key issue to improve the prediction of gene functions. Quite surprisingly only little attention has been devoted to data integration for gene function prediction through ensemble methods. In this work we show that relatively simple ensemble methods are competitive and in some cases are also able to outperform state-of-the-art data integration techniques for gene function prediction

Exploiting Complex Protein Domain Networks for Protein Function Annotation

International audienceHuge numbers of protein sequences are now available in public databases. In order to exploit more fully this valuable biological data, these sequences need to be annotated with functional properties such as Enzyme Commission (EC) numbers and Gene Ontology terms. The UniProt Knowledgebase (UniProtKB) is currently the largest and most comprehensive resource for protein sequence and annotation data. In the March 2018 release of UniProtKB, some 556,000 sequences have been manually curated but over 111 million sequences still lack functional annotations. The ability to annotate automatically these unannotated sequences would represent a major advance for the field of bioinformatics. Here, we present a novel network-based approach called GrAPFI for the automatic functional annotation of protein sequences. The underlying assumption of GrAPFI is that proteins may be related to each other by the protein domains, families, and super-families that they share. Several protein domain databases exist such as In-terPro, Pfam, SMART, CDD, Gene3D, and Prosite, for example. Our approach uses Interpro domains, because the InterPro database contains information from several other major protein family and domain databases. Our results show that GrAPFI achieves better EC number annotation performance than several other previously described approaches

Functional Annotation of Proteins using Domain Embedding based Sequence Classification

International audienceDue to the recent advancement in genomic sequencing technologies, the number of protein sequences in public databases is growing exponentially. The UniProt Knowledgebase (UniProtKB) is currently the largest and most comprehensive resource for protein sequence and annotation data. The May 2019 release of the Uniprot Knowledge base (UniprotKB) contains around 158 million protein sequences. For the complete exploitation of this huge knowledge base, protein sequences need to be annotated with functional properties such as Enzyme Commission (EC) numbers and Gene Ontology terms. However, there is only about half a million sequences (UniprotKB/SwissProt) are reviewed and functionally annotated by expert curators using information extracted from the published literature and computational analyses. The manual annotation by experts are expensive, slow and insufficient to fill the gap between the annotated and unannotated protein sequences. In this paper, we present an automatic functional annotation technique using neural network based based word embedding exploiting domain and family information of proteins. Domains are the most conserved regions in protein sequences and constitute the building blocks of 3D protein structures. To do the experiment, we used fastText a , a library for learning of word embeddings and text classification developed by Facebook's AI Research lab. The experimental results show that domain embeddings perform much better than k-mer based word embeddings. a https://github.com/facebookresearch/fasttex

mlDEEPre: Multi-Functional Enzyme Function Prediction With Hierarchical Multi-Label Deep Learning

As a great challenge in bioinformatics, enzyme function prediction is a significant step toward designing novel enzymes and diagnosing enzyme-related diseases. Existing studies mainly focus on the mono-functional enzyme function prediction. However, the number of multi-functional enzymes is growing rapidly, which requires novel computational methods to be developed. In this paper, following our previous work, DEEPre, which uses deep learning to annotate mono-functional enzyme's function, we propose a novel method, mlDEEPre, which is designed specifically for predicting the functionalities of multi-functional enzymes. By adopting a novel loss function, associated with the relationship between different labels, and a self-adapted label assigning threshold, mlDEEPre can accurately and efficiently perform multi-functional enzyme prediction. Extensive experiments also show that mlDEEPre can outperform the other methods in predicting whether an enzyme is a mono-functional or a multi-functional enzyme (mono-functional vs. multi-functional), as well as the main class prediction across different criteria. Furthermore, due to the flexibility of mlDEEPre and DEEPre, mlDEEPre can be incorporated into DEEPre seamlessly, which enables the updated DEEPre to handle both mono-functional and multi-functional predictions without human intervention

GrAPFI: predicting enzymatic function of proteins from domain similarity graphs

This work is dedicated to the memory of David W. Ritchie, who recently passed away.International audienceBackground: Thanks to recent developments in genomic sequencing technologies, the number of protein sequences in public databases is growing enormously. To enrich and exploit this immensely valuable data, it is essential to annotate these sequences with functional properties such as Enzyme Commission (EC) numbers, for example. The January 2019 release of the Uniprot Knowledge base (UniprotKB) contains around 140 million protein sequences. However, only about half of a million of these (UniprotKB/SwissProt) have been reviewed and functionally annotated by expert curators using data extracted from the literature and computational analyses. To reduce the gap between the annotated and unannotated protein sequences, it is essential to develop accurate automatic protein function annotation techniques. Results: In this work, we present GrAPFI (Graph-based Automatic Protein Function Inference) for automatically annotating proteins with EC number functional descriptors from a protein domain similarity graph. We validated the performance of GrAPFI using six reference proteomes in UniprotKB/SwissProt, namely Human, Mouse, Rat, Yeast, E. Coli and Arabidopsis thaliana. We also compared GrAPFI with existing EC prediction approaches such as ECPred, DEEPre, and SVMProt. This shows that GrAPFI achieves better accuracy and comparable or better coverage with respect to these earlier approaches. Conclusions: GrAPFI is a novel protein function annotation tool that performs automatic inference on a network of proteins that are related according to their domain composition. Our evaluation of GrAPFI shows that it gives better performance than other state of the art methods. GrAPFI is available at https://gitlab.inria.fr/bsarker/bmc_grapfi.git as a stand alone tool written in Python