A sex-dependent computer-aided diagnosis system for autism spectrum disorder using connectivity of resting-state fMRI.

Objective.Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder with the main symptoms of social communication disabilities. ASD is more than four times more common among males than females. The diagnosis of ASD is currently a subjective process by experts the same for males and females. Various studies have suggested the use of brain connectivity features for the diagnosis of ASD. Also, sex-related biological factors have been shown to play a role in ASD etiology and influence the brain connectivity. Therefore, proposing an accurate computer-aided diagnosis system (CADS) for ASD which considers the sex of subjects seems necessary. In this study, we present a sex-dependent connectivity-based CADS for ASD using resting-state functional magnetic resonance imaging. The proposed CADS classifies ASD males from normal males, and ASD females from normal females.Approach.After data preprocessing, group independent component analysis (GICA) was applied to obtain the resting-state networks (RSNs) followed by applying dual-regression to obtain the time course of each RSN for each subject. Afterwards, functional connectivity measures of full correlation and partial correlation and the effective connectivity measure of bivariate Granger causality were computed between time series of RSNs. To consider the role of sex differences in the classification process, male, female, and mixed groups were taken into account, and feature selection and classification were designed for each sex group separately. At the end, the classification accuracy was computed for each sex group.Main results.In the female group, a classification accuracy of 93.3% was obtained using full correlation while in the male group, a classification accuracy of 86.7% was achieved using both full correlation and bivariate Granger causality. Also, in the mixed group, a classification accuracy of 83.3% was obtained using full correlation.Significance.This supports the importance of considering sex in diagnosing ASD patients from normal controls.

Determining the adjusted initial treatment dose of warfarin anticoagulant medicine using kernel-based support vector regression.

BACKGROUND AND OBJECTIVE: A novel research field in bioinformatics is pharmacogenomics and the corresponding applications of artificial intelligence tools. Pharmacogenomics is the study of the relationship between genotype and responses to medical measures such as drug use. One of the most effective drugs is warfarin anticoagulant, but determining its initial treatment dose is challenging. Mistakes in the determination of the initial treatment dose can result directly in patient death. METHODS: Some of the most successful techniques for estimating the initial treatment dose are kernel-based methods. However, all the available studies use pre-defined and constant kernels that might not necessarily address the problem's intended requirements. The present study seeks to define and present a new computational kernel extracted from a data set. This process aims to utilize all the data-related statistical features to generate a dose determination tool proportional to the data set with minimum error rate. The kernel-based version of the least square support vector regression estimator was defined. Through this method, a more appropriate approach was proposed for predicting the adjusted dose of warfarin. RESULTS AND CONCLUSION: This paper benefits from the International Warfarin Pharmacogenomics Consortium (IWPC) Database. The results obtained in this study demonstrate that the support vector regression with the proposed new kernel can successfully estimate the ideal dosage of warfarin for approximately 68% of patients.

Functional Networks Abnormalities in Autism Spectrum Disorder: Age-Related Hypo and Hyper Connectivity.

Autism spectrum disorder (ASD) is a developmental disorder characterized by defects in social interaction. The past functional connectivity studies using resting-state fMRI have found both patterns of hypo-connectivity and hyper-connectivity in ASD and proposed the age as an important factor on functional connectivity disorders. However, this influence is not clearly characterized yet. Previous studies have often examined the functional connectivity disorders in particular brain regions in an age group or a mixture of age groups. The present study compares whole-brain within-connectivity and between-connectivity between ASD individuals and typically developing (TD) controls in three age groups including children (< 11 years), adolescents (11-18 years), and adults (> 18 years), each comprising 21 ASD individuals and 21 TD controls. The age groups were matched for age, Full IQ, and gender. Independent component analysis and dual regression were used to investigate within-connectivity. The full and partial correlations between ICs were used to investigate between-connectivity. Examination of the within-connectivity showed hyper-connectivity, especially in cerebellum and brainstem in ASD children but both hyper/hypo connectivity in adolescents and ASD adults. In ASD children, difference in the between-connectivity among default mode network (DMN), salience-executive network and fronto-parietal network were observed. There was also a negative correlation between DMN and temporal network. Full correlation comparison between ASD adolescents and TD individuals showed significant differences between cerebellum and DMN. Our results supported just the hyper-connectivity in childhood, but both hypo and hyper-connectivity after childhood and hypothesized that abnormal resting connections in ASD exist in the regions of the brain known to be involved in social cognition.

Prediction of Protein Sub-Mitochondria Locations Using Protein Interaction Networks.

BACKGROUND: Prediction of the protein localization is among the most important issues in the bioinformatics that is used for the prediction of the proteins in the cells and organelles such as mitochondria. In this study, several machine learning algorithms are applied for the prediction of the intracellular protein locations. These algorithms use the features extracted from protein sequences. In contrast, protein interactions have been less investigated. OBJECTIVES: As protein interactions usually occur in the same or adjacent places, using this feature to find the location would be efficient and impressive. This study did not aim at increasing the total accuracy of the conducted research. The study has focused on the features of the proteins' interaction and their employment which lead to a higher accuracy. MATERIALS AND METHODS: In this study, we have examined the protein interaction network as one of the features for prediction of the protein localization and its effects on the prediction results. In this regards, we have gathered some of the most common features including Amino Acid Composition, Dipeptide Compositions, Pseudo Amino Acid Compositions (PseAAC), Position Specific Scoring Matrix (PSSM), Functional Domain, Gene Ontology information, and the Pair-wise sequence alignment. The results of the classification are compared to the ones using protein interactions. For achieving this goal different machine learning algorithms were tested. RESULTS: The best-obtained results of using single feature set obtained using SVM classifier for PseAAC feature. The accuracy of combining all features with PPI data, using the Decision Tree and Random Forest classifiers, was 82.49% and 83.35%, respectively. In another experiment, using just protein interaction data with the different cutting points resulted in obtaining an accuracy of 93.035% for the protein location prediction. CONCLUSION: In total, it was shown that protein(s) interaction has a significant impact on the prediction of the mitochondrial proteins' location. This feature can separately distinguish the locations well. Using this feature the accuracy of the results is raised up to 5%.

Dynamical analysis of yeast protein interaction network during the sake brewing process.

Proteins interact with each other for performing essential functions of an organism. They change partners to get involved in various processes at different times or locations. Studying variations of protein interactions within a specific process would help better understand the dynamic features of the protein interactions and their functions. We studied the protein interaction network of Saccharomyces cerevisiae (yeast) during the brewing of Japanese sake. In this process, yeast cells are exposed to several stresses. Analysis of protein interaction networks of yeast during this process helps to understand how protein interactions of yeast change during the sake brewing process. We used gene expression profiles of yeast cells for this purpose. Results of our experiments revealed some characteristics and behaviors of yeast hubs and non-hubs and their dynamical changes during the brewing process. We found that just a small portion of the proteins (12.8 to 21.6%) is responsible for the functional changes of the proteins in the sake brewing process. The changes in the number of edges and hubs of the yeast protein interaction networks increase in the first stages of the process and it then decreases at the final stages.

Features analysis for identification of date and party hubs in protein interaction network of Saccharomyces Cerevisiae.

BACKGROUND: It has been understood that biological networks have modular organizations which are the sources of their observed complexity. Analysis of networks and motifs has shown that two types of hubs, party hubs and date hubs, are responsible for this complexity. Party hubs are local coordinators because of their high co-expressions with their partners, whereas date hubs display low co-expressions and are assumed as global connectors. However there is no mutual agreement on these concepts in related literature with different studies reporting their results on different data sets. We investigated whether there is a relation between the biological features of Saccharomyces Cerevisiae's proteins and their roles as non-hubs, intermediately connected, party hubs, and date hubs. We propose a classifier that separates these four classes. RESULTS: We extracted different biological characteristics including amino acid sequences, domain contents, repeated domains, functional categories, biological processes, cellular compartments, disordered regions, and position specific scoring matrix from various sources. Several classifiers are examined and the best feature-sets based on average correct classification rate and correlation coefficients of the results are selected. We show that fusion of five feature-sets including domains, Position Specific Scoring Matrix-400, cellular compartments level one, and composition pairs with two and one gaps provide the best discrimination with an average correct classification rate of 77%. CONCLUSIONS: We study a variety of known biological feature-sets of the proteins and show that there is a relation between domains, Position Specific Scoring Matrix-400, cellular compartments level one, composition pairs with two and one gaps of Saccharomyces Cerevisiae's proteins, and their roles in the protein interaction network as non-hubs, intermediately connected, party hubs and date hubs. This study also confirms the possibility of predicting non-hubs, party hubs and date hubs based on their biological features with acceptable accuracy. If such a hypothesis is correct for other species as well, similar methods can be applied to predict the roles of proteins in those species.