Author-sourced capture of pathway knowledge in computable form using Biofactoid.

Making the knowledge contained in scientific papers machine-readable and formally computable would allow researchers to take full advantage of this information by enabling integration with other knowledge sources to support data analysis and interpretation. Here we describe Biofactoid, a web-based platform that allows scientists to specify networks of interactions between genes, their products, and chemical compounds, and then translates this information into a representation suitable for computational analysis, search and discovery. We also report the results of a pilot study to encourage the wide adoption of Biofactoid by the scientific community.

Pathway Commons 2019 Update: integration, analysis and exploration of pathway data.

Pathway Commons (https://www.pathwaycommons.org) is an integrated resource of publicly available information about biological pathways including biochemical reactions, assembly of biomolecular complexes, transport and catalysis events and physical interactions involving proteins, DNA, RNA, and small molecules (e.g. metabolites and drug compounds). Data is collected from multiple providers in standard formats, including the Biological Pathway Exchange (BioPAX) language and the Proteomics Standards Initiative Molecular Interactions format, and then integrated. Pathway Commons provides biologists with (i) tools to search this comprehensive resource, (ii) a download site offering integrated bulk sets of pathway data (e.g. tables of interactions and gene sets), (iii) reusable software libraries for working with pathway information in several programming languages (Java, R, Python and Javascript) and (iv) a web service for programmatically querying the entire dataset. Visualization of pathways is supported using the Systems Biological Graphical Notation (SBGN). Pathway Commons currently contains data from 22 databases with 4794 detailed human biochemical processes (i.e. pathways) and ∼2.3 million interactions. To enhance the usability of this large resource for end-users, we develop and maintain interactive web applications and training materials that enable pathway exploration and advanced analysis.

Pattern search in BioPAX models.

MOTIVATION: BioPAX is a standard language for representing complex cellular processes, including metabolic networks, signal transduction and gene regulation. Owing to the inherent complexity of a BioPAX model, searching for a specific type of subnetwork can be non-trivial and difficult. RESULTS: We developed an open source and extensible framework for defining and searching graph patterns in BioPAX models. We demonstrate its use with a sample pattern that captures directed signaling relations between proteins. We provide search results for the pattern obtained from the Pathway Commons database and compare these results with the current data in signaling databases SPIKE and SignaLink. Results show that a pattern search in public pathway data can identify a substantial amount of signaling relations that do not exist in signaling databases. AVAILABILITY: BioPAX-pattern software was developed in Java. Source code and documentation is freely available at http://code.google.com/p/biopax-pattern under Lesser GNU Public License.

Using biological pathway data with paxtools.

A rapidly growing corpus of formal, computable pathway information can be used to answer important biological questions including finding non-trivial connections between cellular processes, identifying significantly altered portions of the cellular network in a disease state and building predictive models that can be used for precision medicine. Due to its complexity and fragmented nature, however, working with pathway data is still difficult. We present Paxtools, a Java library that contains algorithms, software components and converters for biological pathways represented in the standard BioPAX language. Paxtools allows scientists to focus on their scientific problem by removing technical barriers to access and analyse pathway information. Paxtools can run on any platform that has a Java Runtime Environment and was tested on most modern operating systems. Paxtools is open source and is available under the Lesser GNU public license (LGPL), which allows users to freely use the code in their software systems with a requirement for attribution. Source code for the current release (4.2.0) can be found in Software S1. A detailed manual for obtaining and using Paxtools can be found in Protocol S1. The latest sources and release bundles can be obtained from biopax.org/paxtools.

The BioPAX Validator.

SUMMARY: BioPAX is a community-developed standard language for biological pathway data. A key functionality required for efficient BioPAX data exchange is validation-detecting errors and inconsistencies in BioPAX documents. The BioPAX Validator is a command-line tool, Java library and online web service for BioPAX that performs >100 classes of consistency checks. AVAILABILITY AND IMPLEMENTATION: The validator recognizes common syntactic errors and semantic inconsistencies and reports them in a customizable human readable format. It can also automatically fix some errors and normalize BioPAX data. Since its release, the validator has become a critical tool for the pathway informatics community, detecting thousands of errors and helping substantially increase the conformity and uniformity of BioPAX-formatted data. The BioPAX Validator is open source and released under LGPL v3 license. All sources, binaries and documentation can be found at sf.net/p/biopax, and the latest stable version of the web application is available at biopax.org/validator.

Pathway Commons, a web resource for biological pathway data.

Pathway Commons (http://www.pathwaycommons.org) is a collection of publicly available pathway data from multiple organisms. Pathway Commons provides a web-based interface that enables biologists to browse and search a comprehensive collection of pathways from multiple sources represented in a common language, a download site that provides integrated bulk sets of pathway information in standard or convenient formats and a web service that software developers can use to conveniently query and access all data. Database providers can share their pathway data via a common repository. Pathways include biochemical reactions, complex assembly, transport and catalysis events and physical interactions involving proteins, DNA, RNA, small molecules and complexes. Pathway Commons aims to collect and integrate all public pathway data available in standard formats. Pathway Commons currently contains data from nine databases with over 1400 pathways and 687,000 interactions and will be continually expanded and updated.

The BioPAX community standard for pathway data sharing.

Biological Pathway Exchange (BioPAX) is a standard language to represent biological pathways at the molecular and cellular level and to facilitate the exchange of pathway data. The rapid growth of the volume of pathway data has spurred the development of databases and computational tools to aid interpretation; however, use of these data is hampered by the current fragmentation of pathway information across many databases with incompatible formats. BioPAX, which was created through a community process, solves this problem by making pathway data substantially easier to collect, index, interpret and share. BioPAX can represent metabolic and signaling pathways, molecular and genetic interactions and gene regulation networks. Using BioPAX, millions of interactions, organized into thousands of pathways, from many organisms are available from a growing number of databases. This large amount of pathway data in a computable form will support visualization, analysis and biological discovery.

CCancer: a bird's eye view on gene lists reported in cancer-related studies.

CCancer is an automatically collected database of gene lists, which were reported mostly by experimental studies in various biological and clinical contexts. At the moment, the database covers 3369 gene lists extracted from 2644 papers published in approximately 80 peer-reviewed journals. As input, CCancer accepts a gene list. An enrichment analyses is implemented to generate, as output, a highly informative survey over recently published studies that report gene lists, which significantly intersect with the query gene list. A report on gene pairs from the input list which were frequently reported together by other biological studies is also provided. CCancer is freely available at http://mips.helmholtz-muenchen.de/proj/ccancer.

PPI spider: a tool for the interpretation of proteomics data in the context of protein-protein interaction networks.

Recent advances in experimental technologies allow for the detection of a complete cell proteome. Proteins that are expressed at a particular cell state or in a particular compartment as well as proteins with differential expression between various cells states are commonly delivered by many proteomics studies. Once a list of proteins is derived, a major challenge is to interpret the identified set of proteins in the biological context. Protein-protein interaction (PPI) data represents abundant information that can be employed for this purpose. However, these data have not yet been fully exploited due to the absence of a methodological framework that can integrate this type of information. Here, we propose to infer a network model from an experimentally identified protein list based on the available information about the topology of the global PPI network. We propose to use a Monte Carlo simulation procedure to compute the statistical significance of the inferred models. The method has been implemented as a freely available web-based tool, PPI spider (http://mips.helmholtz-muenchen.de/proj/ppispider). To support the practical significance of PPI spider, we collected several hundreds of recently published experimental proteomics studies that reported lists of proteins in various biological contexts. We reanalyzed them using PPI spider and demonstrated that in most cases PPI spider could provide statistically significant hypotheses that are helpful for understanding of the protein list.

Beyond the 'best' match: machine learning annotation of protein sequences by integration of different sources of information.

MOTIVATION: Accurate automatic assignment of protein functions remains a challenge for genome annotation. We have developed and compared the automatic annotation of four bacterial genomes employing a 5-fold cross-validation procedure and several machine learning methods. RESULTS: The analyzed genomes were manually annotated with FunCat categories in MIPS providing a gold standard. Features describing a pair of sequences rather than each sequence alone were used. The descriptors were derived from sequence alignment scores, InterPro domains, synteny information, sequence length and calculated protein properties. Following training we scored all pairs from the validation sets, selected a pair with the highest predicted score and annotated the target protein with functional categories of the prototype protein. The data integration using machine-learning methods provided significantly higher annotation accuracy compared to the use of individual descriptors alone. The neural network approach showed the best performance. The descriptors derived from the InterPro domains and sequence similarity provided the highest contribution to the method performance. The predicted annotation scores allow differentiation of reliable versus non-reliable annotations. The developed approach was applied to annotate the protein sequences from 180 complete bacterial genomes. AVAILABILITY: The FUNcat Annotation Tool (FUNAT) is available on-line as Web Services at http://mips.gsf.de/proj/funat.