A Global Analysis of Enzyme Compartmentalization to Glycosomes

In kinetoplastids, the first seven steps of glycolysis are compartmentalized into a glycosome along with parts of other metabolic pathways. This organelle shares a common ancestor with the better-understood eukaryotic peroxisome. Much of our understanding of the emergence, evolution, and maintenance of glycosomes is limited to explorations of the dixenous parasites, including the enzymatic contents of the organelle. Our objective was to determine the extent that we could leverage existing studies in model kinetoplastids to determine the composition of glycosomes in species lacking evidence of experimental localization. These include diverse monoxenous species and dixenous species with very different hosts. For many of these, genome or transcriptome sequences are available. Our approach initiated with a meta-analysis of existing studies to generate a subset of enzymes with highest evidence of glycosome localization. From this dataset we extracted the best possible glycosome signal peptide identification scheme for in silico identification of glycosomal proteins from any kinetoplastid species. Validation suggested that a high glycosome localization score from our algorithm would be indicative of a glycosomal protein. We found that while metabolic pathways were consistently represented across kinetoplastids, individual proteins within those pathways may not universally exhibit evidence of glycosome localization.

Pioneering Methods for Enhancing PPI and Phenotype Networks for Candidate Disease Prioritization

The physical contacts of high-specificity between two or more protein molecules constitute Protein-Protein Interactions (PPIs). PPI networks are modeled through graphs where node denotes proteins and edges denote interaction between proteins. The PPI network plays an important role to identify the interesting disease gene candidates. But, the PPI network usually contains false interactions. Many techniques have been proposed to reconstruct PPI network to remove false interactions and improve ranking of candidate disease. Random Walk with Restart on Diffusion profile (RWRDP) and Random Walk on a Reliable Heterogeneous Network (RWRHN) was two among them. In these methods, Gene topological similarity was incorporated with original PPI network to reconstruct new PPI network. Phenotype network was constructed by calculating similarity between gene phenotypes. The reconstructed network and phenotype networks were combined to rank candidate disease genes. However, the PPI reconstruction was fully related with the quality of protein interaction data. In order to enhance the reconstruction of PPI, a Piecewise Linear Regression (PLR) based protein sequence similarity measure and Bat Algorithm based gene expression similarity were proposed with RHN. In this paper, additional measure called Interaction Level Sub cellular Localization Score (ILSLS) is proposed to further reduce the false interaction in the reconstruction of PPI network. ILSLS is the combination of Normalized Sub cellular Localization score (NSL) and Protein Multiple Location Prediction score (PMLP). The proposed work is named as Random Walker on Optimized Trustworthy Heterogeneous Sub Cellular localization aware Network (RW-OTHSN). In order to enhance the ranking of RWOTHSN, phenotype structure is considered while construction phenotype network to rank the candidate disease genes. The phenotype structure is characterized based on h*-sequence model which identify highly discriminative signatures with only a small number of genes. This proposed work is named as Random Walker on Optimized Trustworthy Heterogeneous Sub Cellular localization and Phenotype structure aware Network (RWOTHSPN). The efficiency of the proposed methods are evaluated on PPI network database in terms of Average degree, Relative Frequency for PPI reconstruction, Number of successful predictions, precision and recall for candidate disease gene ranking.

S222 – Sound Localization in Subjects with Tinnitus

Objectives Sound localization in subjects with normal hearing is done by recognition of interaural difference of time, intensity, and phase of sound source. The defect of sound localizing ability may increase the chance of accident, decrease public conversation. Individuals with tinnitus, deprived of the binaural cues, are expected to have difficulty in localizing sound. The purpose of the research is to investigate the sound localizing ability in subjects with tinnitus to localize sound in horizontal plane by comparing with normal control group. Methods 3 groups of subjects participated in this study. The first group consisted of 30 subjects with unilateral tinnitus without hearing disturbance, the second group consisted of 30 subjects with unilateral tinntus, hearing disturbance. Control group was 20 normal hearing adults. Sound localization ability was assessed by means of an array of 8 loudspeakers positioned at the azimuth of 45°each in the horizontal plane at a distance of 100 cm from the subject. Results The localization score increased significantly as tinnitus with hearing disturbance as compared with control group(p<0.05). In the tinnitus without hearing disturbance group as compared with the control group, the localization score increased but there is no stastical significance. Conclusions In the tinnitus without hearing disturbance group, the sound localization ability was decreased but there is no stastical significance. This means that tinnitus has relatively small effect of interaural intensity difference in usual living. It needs further study with similar tinnitus intensity, pitch.