Deep proteogenomics; high throughput gene validation by multidimensional liquid chromatography and mass spectrometry of proteins from the fungal wheat pathogen Stagonospora nodorum

BACKGROUND: Stagonospora nodorum, a fungal ascomycete in the class dothideomycetes, is a damaging pathogen of wheat. It is a model for necrotrophic fungi that cause necrotic symptoms via the interaction of multiple effector proteins with cultivar-specific receptors. A draft genome sequence and annotation was published in 2007. A second-pass gene prediction using a training set of 795 fully EST-supported genes predicted a total of 10762 version 2 nuclear-encoded genes, with an additional 5354 less reliable version 1 genes also retained. RESULTS: In this study, we subjected soluble mycelial proteins to proteolysis followed by 2D LC MALDI-MS/MS. Comparison of the detected peptides with the gene models validated 2134 genes. 62% of these genes (1324) were not supported by prior EST evidence. Of the 2134 validated genes, all but 188 were version 2 annotations. Statistical analysis of the validated gene models revealed a preponderance of cytoplasmic and nuclear localised proteins, and proteins with intracellularassociated GO terms. These statistical associations are consistent with the source of the peptides used in the study. Comparison with a 6-frame translation of the S. nodorum genome assembly confirmed 905 existing gene annotations (including 119 not previously confirmed) and provided evidence supporting 144 genes with coding exon frameshift modifications, 604 genes with extensions of coding exons into annotated introns or untranslated regions (UTRs), 3 new gene annotations which were supported by tblastn to NR, and 44 potential new genes residing within un-assembled regions of the genome. CONCLUSION: We conclude that 2D LC MALDI-MS/MS is a powerful, rapid and economical tool to aid in the annotation of fungal genomic assemblies

WholePathwayScope: a comprehensive pathway-based analysis tool for high-throughput data

BACKGROUND: Analysis of High Throughput (HTP) Data such as microarray and proteomics data has provided a powerful methodology to study patterns of gene regulation at genome scale. A major unresolved problem in the post-genomic era is to assemble the large amounts of data generated into a meaningful biological context. We have developed a comprehensive software tool, WholePathwayScope (WPS), for deriving biological insights from analysis of HTP data. RESULT: WPS extracts gene lists with shared biological themes through color cue templates. WPS statistically evaluates global functional category enrichment of gene lists and pathway-level pattern enrichment of data. WPS incorporates well-known biological pathways from KEGG (Kyoto Encyclopedia of Genes and Genomes) and Biocarta, GO (Gene Ontology) terms as well as user-defined pathways or relevant gene clusters or groups, and explores gene-term relationships within the derived gene-term association networks (GTANs). WPS simultaneously compares multiple datasets within biological contexts either as pathways or as association networks. WPS also integrates Genetic Association Database and Partial MedGene Database for disease-association information. We have used this program to analyze and compare microarray and proteomics datasets derived from a variety of biological systems. Application examples demonstrated the capacity of WPS to significantly facilitate the analysis of HTP data for integrative discovery. CONCLUSION: This tool represents a pathway-based platform for discovery integration to maximize analysis power. The tool is freely available at

Patient Specific Congestive Heart Failure Detection From Raw ECG signal

In this study; in order to diagnose congestive heart failure (CHF) patients, non-linear second-order difference plot (SODP) obtained from raw 256 Hz sampled frequency and windowed record with different time of ECG records are used. All of the data rows are labelled with their belongings to classify much more realistically. SODPs are divided into different radius of quadrant regions and numbers of the points fall in the quadrants are computed in order to extract feature vectors. Fisher's linear discriminant, Naive Bayes, Radial basis function, and artificial neural network are used as classifier. The results are considered in two step validation methods as general k-fold cross-validation and patient based cross-validation. As a result, it is shown that using neural network classifier with features obtained from SODP, the constructed system could distinguish normal and CHF patients with 100% accuracy rate. KeywordsComment: Congestive heart failure, ECG, Second-Order Difference Plot, classification, patient based cross-validatio

Traumatic Brain Injury Induces Genome-Wide Transcriptomic, Methylomic, and Network Perturbations in Brain and Blood Predicting Neurological Disorders.

The complexity of the traumatic brain injury (TBI) pathology, particularly concussive injury, is a serious obstacle for diagnosis, treatment, and long-term prognosis. Here we utilize modern systems biology in a rodent model of concussive injury to gain a thorough view of the impact of TBI on fundamental aspects of gene regulation, which have the potential to drive or alter the course of the TBI pathology. TBI perturbed epigenomic programming, transcriptional activities (expression level and alternative splicing), and the organization of genes in networks centered around genes such as Anax2, Ogn, and Fmod. Transcriptomic signatures in the hippocampus are involved in neuronal signaling, metabolism, inflammation, and blood function, and they overlap with those in leukocytes from peripheral blood. The homology between genomic signatures from blood and brain elicited by TBI provides proof of concept information for development of biomarkers of TBI based on composite genomic patterns. By intersecting with human genome-wide association studies, many TBI signature genes and network regulators identified in our rodent model were causally associated with brain disorders with relevant link to TBI. The overall results show that concussive brain injury reprograms genes which could lead to predisposition to neurological and psychiatric disorders, and that genomic information from peripheral leukocytes has the potential to predict TBI pathogenesis in the brain

Dimension Reduction by Mutual Information Discriminant Analysis

In the past few decades, researchers have proposed many discriminant analysis (DA) algorithms for the study of high-dimensional data in a variety of problems. Most DA algorithms for feature extraction are based on transformations that simultaneously maximize the between-class scatter and minimize the withinclass scatter matrices. This paper presents a novel DA algorithm for feature extraction using mutual information (MI). However, it is not always easy to obtain an accurate estimation for high-dimensional MI. In this paper, we propose an efficient method for feature extraction that is based on one-dimensional MI estimations. We will refer to this algorithm as mutual information discriminant analysis (MIDA). The performance of this proposed method was evaluated using UCI databases. The results indicate that MIDA provides robust performance over different data sets with different characteristics and that MIDA always performs better than, or at least comparable to, the best performing algorithms.Comment: 13pages, 3 tables, International Journal of Artificial Intelligence & Application

Structural health monitoring of offshore wind turbines: A review through the Statistical Pattern Recognition Paradigm

Offshore Wind has become the most profitable renewable energy source due to the remarkable development it has experienced in Europe over the last decade. In this paper, a review of Structural Health Monitoring Systems (SHMS) for offshore wind turbines (OWT) has been carried out considering the topic as a Statistical Pattern Recognition problem. Therefore, each one of the stages of this paradigm has been reviewed focusing on OWT application. These stages are: Operational Evaluation; Data Acquisition, Normalization and Cleansing; Feature Extraction and Information Condensation; and Statistical Model Development. It is expected that optimizing each stage, SHMS can contribute to the development of efficient Condition-Based Maintenance Strategies. Optimizing this strategy will help reduce labor costs of OWTs׳ inspection, avoid unnecessary maintenance, identify design weaknesses before failure, improve the availability of power production while preventing wind turbines׳ overloading, therefore, maximizing the investments׳ return. In the forthcoming years, a growing interest in SHM technologies for OWT is expected, enhancing the potential of offshore wind farm deployments further offshore. Increasing efficiency in operational management will contribute towards achieving UK׳s 2020 and 2050 targets, through ultimately reducing the Levelised Cost of Energy (LCOE)

The Fisher Hypothesis and the Forecastability and Persistence of Inflation

For the period 1860 to 1939, the simple correlation of the U.S. commercial paper rate with the contemporaneous inflation rate is -.17. The corresponding correlation for the period 1950 to 1979 is .71. Inflation evolved from essentially a white noise process in the pre-World War I years to a highly persistent, nonstationary ARIMA process in the post-1960 period. I argue that the appearance of an ex post Fisher effect for the first time after 1960 reflects this change in the stochastic process of inflation, rather than a change in any structural relationship between nominal rates and expectedi nflation. I find little evidence of inflation non-neutrality in data from the gold standard period.This contradicts the conclusion of a frequently cited study by Lawrence Summers, who examined the low frequency relationship between inflation and interest rates using band spectrum regression. Deriving and implementing a frequency domain version of the Theil misspecification theorem, I find that neither high frequency nor low frequency movements in gold standard inflation rates were forecastable. Thus even if nominal rates responded fully to expected inflation, one would expect to find the zero coefficient obtained by Summers.

Methods for interpreting lists of affected genes obstained in a DNA microarray experiment

Background - The aim of this paper was to describe and compare the methods used and the results obtained by the participants in a joint EADGENE (European Animal Disease Genomic Network of Excellence) and SABRE (Cutting Edge Genomics for Sustainable Animal Breeding) workshop focusing on post analysis of microarray data. The participating groups were provided with identical lists of microarray probes, including test statistics for three different contrasts, and the normalised log-ratios for each array, to be used as the starting point for interpreting the affected probes. The data originated from a microarray experiment conducted to study the host reactions in broilers occurring shortly after a secondary challenge with either a homologous or heterologous species of Eimeria. Results - Several conceptually different analytical approaches, using both commercial and public available software, were applied by the participating groups. The following tools were used: Ingenuity Pathway Analysis, MAPPFinder, LIMMA, GOstats, GOEAST, GOTM, Globaltest, TopGO, ArrayUnlock, Pathway Studio, GIST and AnnotationDbi. The main focus of the approaches was to utilise the relation between probes/genes and their gene ontology and pathways to interpret the affected probes/genes. The lack of a well-annotated chicken genome did though limit the possibilities to fully explore the tools. The main results from these analyses showed that the biological interpretation is highly dependent on the statistical method used but that some common biological conclusions could be reached. Conclusion - It is highly recommended to test different analytical methods on the same data set and compare the results to obtain a reliable biological interpretation of the affected genes in a DNA microarray experimen