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Various algorithmic and statistical approaches have been proposed to uncover functionally coherent network motifs consisting of sets of genes that may occur as compensatory pathways (called Between Pathway Modules, or BPMs) in a high-throughput S. Cerevisiae genetic interaction network. We extend our previous Local-Cut/Genecentric method to also make use of a spectral clustering of the physical interaction network, and uncover some interesting new fault-tolerant modules. 

Coral reefs are home to over two million species and provide habitat for roughly 25% of all marine animals, but they are being severely threatened by pollution and climate change. A large amount of genomic, transcriptomic, and other omics data is becoming increasingly available from different species of reef-building corals, the unicellular dinoflagellates, and the coral microbiome (bacteria, archaea, viruses, fungi, etc.). Such new data present an opportunity for bioinformatics researchers and computational biologists to contribute to a timely, compelling, and urgent investigation of critical factors that influence reef health and resilience. 

Abstract 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. 

Protein function prediction, based on the patterns of connection in a protein–protein interaction (or association) network, is perhaps the most studied of the classical, fundamental inference problems for biological networks. A highly successful set of recent approaches use random walk-based low-dimensional embeddings that tend to place functionally similar proteins into coherent spatial regions. However, these approaches lose valuable local graph structure from the network when considering only the embedding. We introduce GLIDER, a method that replaces a protein–protein interaction or association network with a new graph-based similarity network. GLIDER is based on a variant of our previous GLIDE method, which was designed to predict missing links in protein–protein association networks, capturing implicit local and global (i.e. embedding-based) graph properties.

GLIDER outperforms competing methods on the task of predicting GO functional labels in cross-validation on a heterogeneous collection of four human protein–protein association networks derived from the 2016 DREAM Disease Module Identification Challenge, and also on three different protein–protein association networks built from the STRING database. We show that this is due to the strong functional enrichment that is present in the local GLIDER neighborhood in multiple different types of protein–protein association networks. Furthermore, we introduce the GLIDER graph neighborhood as a way for biologists to visualize the local neighborhood of a disease gene. As an application, we look at the local GLIDER neighborhoods of a set of known Parkinson’s Disease GWAS genes, rediscover many genes which have known involvement in Parkinson’s disease pathways, plus suggest some new genes to study.

All code is publicly available and can be accessed here: https://github.com/kap-devkota/GLIDER.

Supplementary data are available at Bioinformatics online.

 

A method to improve protein function prediction for sparsely annotated PPI networks is introduced. The method extends the DSD majority vote algorithm introduced by Cao et al. to give confidence scores on predicted labels and to use predictions of high confidence to predict the labels of other nodes in subsequent rounds. We call this a majority vote cascade. Several cascade variants are tested in a stringent cross-validation experiment on PPI networks from S. cerevisiae and D. melanogaster, and we show that for many different settings with several alternative confidence functions, cascading improves the accuracy of the predictions. A list of the most confident new label predictions in the two networks is also reported. Code and networks for the cross-validation experiments appear at http://bcb.cs.tufts.edu/cascade. 

Abstract Motivation One of the core problems in the analysis of biological networks is the link prediction problem. In particular, existing interactions networks are noisy and incomplete snapshots of the true network, with many true links missing because those interactions have not yet been experimentally observed. Methods to predict missing links have been more extensively studied for social than for biological networks; it was recently argued that there is some special structure in protein–protein interaction (PPI) network data that might mean that alternate methods may outperform the best methods for social networks. Based on a generalization of the diffusion state distance, we design a new embedding-based link prediction method called global and local integrated diffusion embedding (GLIDE). GLIDE is designed to effectively capture global network structure, combined with alternative network type-specific customized measures that capture local network structure. We test GLIDE on a collection of three recently curated human biological networks derived from the 2016 DREAM disease module identification challenge as well as a classical version of the yeast PPI network in rigorous cross validation experiments. Results We indeed find that different local network structure is dominant in different types of biological networks. We find that the simple local network measures are dominant in the highly connected network core between hub genes, but that GLIDE’s global embedding measure adds value in the rest of the network. For example, we make GLIDE-based link predictions from genes known to be involved in Crohn’s disease, to genes that are not known to have an association, and make some new predictions, finding support in other network data and the literature. Availability and implementation GLIDE can be downloaded at https://bitbucket.org/kap_devkota/glide. Supplementary information Supplementary data are available at Bioinformatics online. 

A method to improve protein function prediction for sparsely annotated PPI networks is introduced. The method extends the DSD majority vote algorithm introduced by Cao et al. to give confidence scores on predicted labels and to use predictions of high confidence to predict the labels of other nodes in subsequent rounds. We call this a majority vote cascade. Several cascade variants are tested in a stringent cross-validation experiment on PPI networks from S. cerevisiae and D. melanogaster, and we show that for many different settings with several alternative confidence functions, cascading improves the accuracy of the predictions. A list of the most confident new label predictions in the two networks is also reported. Code, networks for the cross-validation experiments, and supplementary figures and tables appear at http://bcb.cs.tufts.edu/cascade.