Fuzzy measures on the Gene Ontology for gene product similarity

pre-printOne of the most important objects in bioinformatics is a gene product (protein or RNA). For many gene products, functional information is summarized in a set of Gene Ontology (GO) annotations. For these genes, it is reasonable to include similarity measures based on the terms found in the GO or other taxonomy. In this paper, we introduce several novel measures for computing the similarity of two gene products annotated with GO terms. The fuzzy measure similarity (FMS) has the advantage that it takes into consideration the context of both complete sets of annotation terms when computing the similarity between two gene products. When the two gene products are not annotated by common taxonomy terms, we propose a method that avoids a zero similarity result. To account for the variations in the annotation reliability, we propose a similarity measure based on the Choquet integral. These similarity measures provide extra tools for the biologist in search of functional information for gene products. The initial testing on a group of 194 sequences representing three proteins families shows a higher correlation of the FMS and Choquet similarities to the BLAST sequence similarities than the traditional similarity measures such as pairwise average or pairwise maximum

Preparation and characterization of magnetite (Fe3O4) nanoparticles By Sol-Gel method

The magnetite (Fe3O4) nanoparticles were successfully synthesized and annealed under vacuum at different temperature. The Fe3O4 nanoparticles prepared via sol-gel assisted method and annealed at 200-400ºC were characterized by Fourier Transformation Infrared Spectroscopy (FTIR), X-ray Diffraction spectra (XRD), Field Emission Scanning Electron Microscope (FESEM) and Atomic Force Microscopy (AFM). The XRD result indicate the presence of Fe3O4 nanoparticles, and the Scherer`s Formula calculated the mean particles size in range of 2-25 nm. The FESEM result shows that the morphologies of the particles annealed at 400ºC are more spherical and partially agglomerated, while the EDS result indicates the presence of Fe3O4 by showing Fe-O group of elements. AFM analyzed the 3D and roughness of the sample; the Fe3O4 nanoparticles have a minimum diameter of 79.04 nm, which is in agreement with FESEM result. In many cases, the synthesis of Fe3O4 nanoparticles using FeCl3 and FeCl2 has not been achieved, according to some literatures, but this research was able to obtained Fe3O4 nanoparticles base on the characterization results

Mapping from Statistical to Biological Proximity

We verify whether the proximity claimed by state-of-the-art statistical similarity measures are indeed biologically appropriate or not. We present some analytical results on it

SANA NetGO: A combinatorial approach to using Gene Ontology (GO) terms to score network alignments

Gene Ontology (GO) terms are frequently used to score alignments between protein-protein interaction (PPI) networks. Methods exist to measure the GO similarity between two proteins in isolation, but pairs of proteins in a network alignment are not isolated: each pairing is implicitly dependent upon every other pairing via the alignment itself. Current methods fail to take into account the frequency of GO terms across the networks, and attempt to account for common GO terms in an ad hoc fashion by imposing arbitrary rules on when to "allow" GO terms based on their location in the GO hierarchy, rather than using readily available frequency information in the PPI networks themselves. Here we develop a new measure, NetGO, that naturally weighs infrequent, informative GO terms more heavily than frequent, less informative GO terms, without requiring arbitrary cutoffs. In particular, NetGO down-weights the score of frequent GO terms according to their frequency in the networks being aligned. This is a global measure applicable only to alignments, independent of pairwise GO measures, in the same sense that the edge-based EC or S3 scores are global measures of topological similarity independent of pairwise topological similarities. We demonstrate the superiority of NetGO by creating alignments of predetermined quality based on homologous pairs of nodes and show that NetGO correlates with alignment quality much better than any existing GO-based alignment measures. We also demonstrate that NetGO provides a measure of taxonomic similarity between species, consistent with existing taxonomic measures--a feature not shared with existing GO-based network alignment measures. Finally, we re-score alignments produced by almost a dozen aligners from a previous study and show that NetGO does a better job than existing measures at separating good alignments from bad ones

Determining Domain Similarity and Domain-Protein Similarity using Functional Similarity Measurements of Gene Ontology Terms

Protein domains typically correspond to major functional sites of a protein. Therefore, determining similarity between domains can aid in the comparison of protein functions, and can provide a basis for grouping domains based on function. One strategy for comparing domain similarity and domain-protein similarity is to use similarity measurements of annotation terms from the Gene Ontology (GO). In this paper five methods are analyzed in terms of their usefulness for comparing domains, and comparing domains to proteins based on GO terms

The Inferred Cardiogenic Gene Regulatory Network in the Mammalian Heart

Cardiac development is a complex, multiscale process encompassing cell fate adoption, differentiation and morphogenesis. To elucidate pathways underlying this process, a recently developed algorithm to reverse engineer gene regulatory networks was applied to time-course microarray data obtained from the developing mouse heart. Approximately 200 genes of interest were input into the algorithm to generate putative network topologies that are capable of explaining the experimental data via model simulation. To cull specious network interactions, thousands of putative networks are merged and filtered to generate scale-free, hierarchical networks that are statistically significant and biologically relevant. The networks are validated with known gene interactions and used to predict regulatory pathways important for the developing mammalian heart. Area under the precision-recall curve and receiver operator characteristic curve are 9% and 58%, respectively. Of the top 10 ranked predicted interactions, 4 have already been validated. The algorithm is further tested using a network enriched with known interactions and another depleted of them. The inferred networks contained more interactions for the enriched network versus the depleted network. In all test cases, maximum performance of the algorithm was achieved when the purely data-driven method of network inference was combined with a data-independent, functional-based association method. Lastly, the network generated from the list of approximately 200 genes of interest was expanded using gene-profile uniqueness metrics to include approximately 900 additional known mouse genes and to form the most likely cardiogenic gene regulatory network. The resultant network supports known regulatory interactions and contains several novel cardiogenic regulatory interactions. The method outlined herein provides an informative approach to network inference and leads to clear testable hypotheses related to gene regulation

Link communities reveal multiscale complexity in networks

Networks have become a key approach to understanding systems of interacting objects, unifying the study of diverse phenomena including biological organisms and human society. One crucial step when studying the structure and dynamics of networks is to identify communities: groups of related nodes that correspond to functional subunits such as protein complexes or social spheres. Communities in networks often overlap such that nodes simultaneously belong to several groups. Meanwhile, many networks are known to possess hierarchical organization, where communities are recursively grouped into a hierarchical structure. However, the fact that many real networks have communities with pervasive overlap, where each and every node belongs to more than one group, has the consequence that a global hierarchy of nodes cannot capture the relationships between overlapping groups. Here we reinvent communities as groups of links rather than nodes and show that this unorthodox approach successfully reconciles the antagonistic organizing principles of overlapping communities and hierarchy. In contrast to the existing literature, which has entirely focused on grouping nodes, link communities naturally incorporate overlap while revealing hierarchical organization. We find relevant link communities in many networks, including major biological networks such as protein-protein interaction and metabolic networks, and show that a large social network contains hierarchically organized community structures spanning inner-city to regional scales while maintaining pervasive overlap. Our results imply that link communities are fundamental building blocks that reveal overlap and hierarchical organization in networks to be two aspects of the same phenomenon.Comment: Main text and supplementary informatio

Improved human disease candidate gene prioritization using mouse phenotype

<p>Abstract</p> <p>Background</p> <p>The majority of common diseases are multi-factorial and modified by genetically and mechanistically complex polygenic interactions and environmental factors. High-throughput genome-wide studies like linkage analysis and gene expression profiling, tend to be most useful for classification and characterization but do not provide sufficient information to identify or prioritize specific disease causal genes.</p> <p>Results</p> <p>Extending on an earlier hypothesis that the majority of genes that impact or cause disease share membership in any of several functional relationships we, for the first time, show the utility of mouse phenotype data in human disease gene prioritization. We study the effect of different data integration methods, and based on the validation studies, we show that our approach, ToppGene <url>http://toppgene.cchmc.org</url>, outperforms two of the existing candidate gene prioritization methods, SUSPECTS and ENDEAVOUR.</p> <p>Conclusion</p> <p>The incorporation of phenotype information for mouse orthologs of human genes greatly improves the human disease candidate gene analysis and prioritization.</p