Search

Background. Urate crystals-induced inflammation is a critical factor during the initiation of gouty arthritis. Berberine is well known for its anti-inflammatory activity. However, the underlying effects of berberine on monosodium urate crystals-induced inflammation remain obscure. Objectives. This study is set to explore the protective effect and mechanism of berberine on monosodium urate crystals-induced inflammation in human monocytic THP-1 cells. Methods. The mRNA levels of NLRP3 and IL-1β were measured by Real-Time PCR, and the protein levels of NLRP3 and IL-1β were determined by ELISA, Western blot, and immunofluorescence. Results. The NLRP3 and IL-1β expressions were significantly increased in model group compared to that in normal group (P<0.05). Meanwhile, there was significant reduction in the expressions of NLRP3 and IL-1β mRNA in groups 6.25 μM berberine and 25 μM berberine when compared with model group (P<0.05). Conclusions. Therefore, berberine alleviates monosodium urate crystals-induced inflammation by downregulating NLRP3 and IL-1β expressions. The regulatory effects of berberine may be related to the inactivation of NLRP3 inflammasome. [ABSTRACT FROM AUTHOR]

Long-term cigarette smoking causes various human diseases, including respiratory disease, cancer, and gastrointestinal (GI) disorders. Alterations in gene expression and variable splicing processes induced by smoking are associated with the development of diseases. This study applied advanced machine learning methods to identify the isoforms with important roles in distinguishing smokers from former smokers based on the expression profile of isoforms from current and former smokers collected in one previous study. These isoforms were deemed as features, which were first analyzed by the Boruta to select features highly correlated with the target variables. Then, the selected features were evaluated by four feature ranking algorithms, resulting in four feature lists. The incremental feature selection method was applied to each list for obtaining the optimal feature subsets and building high-performance classification models. Furthermore, a series of classification rules were accessed by decision tree with the highest performance. Eventually, the rationality of the mined isoforms (features) and classification rules was verified by reviewing previous research. Features such as isoforms ENST00000464835 (expressed by LRRN3), ENST00000622663 (expressed by SASH1), and ENST00000284311 (expressed by GPR15), and pathways (cytotoxicity mediated by natural killer cell and cytokine–cytokine receptor interaction) revealed by the enrichment analysis, were highly relevant to smoking response, suggesting the robustness of our analysis pipeline. [ABSTRACT FROM AUTHOR]

Sarcoma, the second common type of solid tumor in children and adolescents, has a wide variety of subtypes that are often not properly diagnosed at an early stage, leading to late metastases and causing serious loss of life and property to patients and families. It exhibits a high degree of heterogeneity at the cellular, molecular, and epigenetic levels, where DNA methylation has been proposed to play a role in the diagnosis of sarcoma subtypes. Thus, this study is aimed at finding potential biomarkers at the DNA methylation level to distinguish different sarcoma subtypes. A machine learning process was designed to analyse sarcoma samples, each of which was represented by lots of methylation sites. Irrelevant sites were removed using the Boruta method, and remaining sites related to the target variables were kept for further analyses. Afterward, three feature ranking methods (LASSO, LightGBM, and MCFS) were adopted to rank these features, and six classification models were constructed by combining incremental feature selection and two classification algorithms (decision tree and random forest). Among these models, the performance of RF model was higher than that of DT model under all three ranking conditions. The specific expression of genes obtained from the annotation of highly correlated methylation site features, such as PRKAR1B, INPP5A, and GLI3, was proven to be associated with sarcoma by publications. Moreover, the quantitative rules obtained by decision tree algorithm helped us to understand the essential differences between various sarcoma types and classify sarcoma subtypes, providing a new means of clinical identification and determining new therapeutic targets. [ABSTRACT FROM AUTHOR]

Subcellular localization attempts to assign proteins to one of the cell compartments that performs specific biological functions. Finding the link between proteins, biological functions, and subcellular localization is an effective way to investigate the general organization of living cells in a systematic manner. However, determining the subcellular localization of proteins by traditional experimental approaches is difficult. Here, protein–protein interaction networks, functional enrichment on gene ontology and pathway, and a set of proteins having confirmed subcellular localization were applied to build prediction models for human protein subcellular localizations. To build an effective predictive model, we employed a variety of robust machine learning algorithms, including Boruta feature selection, minimum redundancy maximum relevance, Monte Carlo feature selection, and LightGBM. Then, the incremental feature selection method with random forest and support vector machine was used to discover the essential features. Furthermore, 38 key features were determined by integrating results of different feature selection methods, which may provide critical insights into the subcellular location of proteins. Their biological functions of subcellular localizations were discussed according to recent publications. In summary, our computational framework can help advance the understanding of subcellular localization prediction techniques and provide a new perspective to investigate the patterns of protein subcellular localization and their biological importance. [ABSTRACT FROM AUTHOR]

The cell cycle is composed of a series of ordered, highly regulated processes through which a cell grows and duplicates its genome and eventually divides into two daughter cells. According to the complex changes in cell structure and biosynthesis, the cell cycle is divided into four phases: gap 1 (G1), DNA synthesis (S), gap 2 (G2), and mitosis (M). Determining which cell cycle phases a cell is in is critical to the research of cancer development and pharmacy for targeting cell cycle. However, current detection methods have the following problems: (1) they are complicated and time consuming to perform, and (2) they cannot detect the cell cycle on a large scale. Rapid developments in single-cell technology have made dissecting cells on a large scale possible with unprecedented resolution. In the present research, we construct efficient classifiers and identify essential gene biomarkers based on single-cell RNA sequencing data through Boruta and three feature ranking algorithms (e.g., mRMR, MCFS, and SHAP by LightGBM) by utilizing four advanced classification algorithms. Meanwhile, we mine a series of classification rules that can distinguish different cell cycle phases. Collectively, we have provided a novel method for determining the cell cycle and identified new potential cell cycle-related genes, thereby contributing to the understanding of the processes that regulate the cell cycle. [ABSTRACT FROM AUTHOR]

Nowadays, pollution levels are rapidly increasing all over the world. One of the most important pollutants is PM2.5. It is known that the pollution environment may cause several problems, such as greenhouse effect and acid rain. Among them, the most important problem is that pollutants can induce a number of serious diseases. Some studies have reported that PM2.5 is an important etiologic factor for lung cancer. In this study, we extensively investigate the associations between PM2.5 and 22 disease classes recommended by Goh et al., such as respiratory diseases, cardiovascular diseases, and gastrointestinal diseases. The protein-protein interactions were used to measure the linkage between disease genes and genes that have been reported to be modulated by PM2.5. The results suggest that some diseases, such as diseases related to ear, nose, and throat and gastrointestinal, nutritional, renal, and cardiovascular diseases, are influenced by PM2.5 and some evidences were provided to confirm our results. For example, a total of 18 genes related to cardiovascular diseases are identified to be closely related to PM2.5, and cardiovascular disease relevant gene DSP is significantly related to PM2.5 gene JUP. [ABSTRACT FROM AUTHOR]

Lymphoma is a serious malignant tumor that contains more than 70 different types and seriously endangers the body's lymphatic system. The lymphatic system is the regulatory center of the immune system and is important in the immune response to foreign antigens and tumors. Studies showed that multiple genetic variants are associated with lymphoma but determining the pathogenic mechanisms remains a challenge. In the present study, we first applied the Gene Ontology (GO) and KEGG pathway enrichment analyses of lymphoma-associated and lymphoma-nonassociated genes. Next, the Boruta and max-relevance and min-redundancy feature selection methods were performed to filter and rank features. Then, features preselected and ranked using the incremental feature selection method were applied for the decision tree model to identify the best GO terms and KEGG pathways and extract classification rules. Results indicate that our predicted features, such as B-cell activation, negative regulation of protein processing, negative regulation of mast cell cytokine production, and natural killer cell-mediated cytotoxicity, are associated with the biological process of lymphoma, consistent with those of recent publications. This study provides a new perspective for future research on the molecular mechanisms of lymphoma. [ABSTRACT FROM AUTHOR]

The mechanisms of lung cancer are highly complex. Not only mRNA gene expression but also microRNAs, DNA methylation, and copy number variation (CNV) play roles in tumorigenesis. It is difficult to incorporate so much information into a single model that can comprehensively reflect all these lung cancer mechanisms. In this study, we analyzed the 129 TCGA (The Cancer Genome Atlas) squamous cell lung carcinoma samples with gene expression, microRNA expression, DNA methylation, and CNV data. First, we used variance inflation factor (VIF) regression to build the whole genome integrative network. Then, we isolated the lung cancer subnetwork by identifying the known lung cancer genes and their direct regulators. This subnetwork was refined by the Bayesian method, and the directed regulations among mRNA genes, microRNAs, methylations, and CNVs were obtained. The novel candidate key drivers in this refined subnetwork, such as the methylation of ARHGDIB and HOXD3, microRNA let-7a and miR-31, and the CNV of AGAP2, were identified and analyzed. On three large public available lung cancer datasets, the key drivers ARHGDIB and HOXD3 demonstrated significant associations with the overall survival of lung cancer patients. Our results provide new insights into lung cancer mechanisms. [ABSTRACT FROM AUTHOR]

COVID-19 is hypothesized to be linked to the host's excessive inflammatory immunological response to SARS-CoV-2 infection, which is regarded to be a major factor in disease severity and mortality. Numerous immune cells play a key role in immune response regulation, and gene expression analysis in these cells could be a useful method for studying disease states, assessing immunological responses, and detecting biomarkers. Here, we developed a machine learning procedure to find biomarkers that discriminate disease severity in individual immune cells (B cell, CD4+ cell, CD8+ cell, monocyte, and NK cell) using single-cell gene expression profiles of COVID-19. The gene features of each profile were first filtered and ranked using the Boruta feature selection method and mRMR, and the resulting ranked feature lists were then fed into the incremental feature selection method to determine the optimal number of features with decision tree and random forest algorithms. Meanwhile, we extracted the classification rules in each cell type from the optimal decision tree classifiers. The best gene sets discovered in this study were analyzed by GO and KEGG pathway enrichment, and some important biomarkers like TLR2, ITK, CX3CR1, IL1B, and PRDM1 were validated by recent literature. The findings reveal that the optimal gene sets for each cell type can accurately classify COVID-19 disease severity and provide insight into the molecular mechanisms involved in disease progression. [ABSTRACT FROM AUTHOR]

Methylation is one of the most common and considerable modifications in biological systems mediated by multiple enzymes. Recent studies have shown that methylation has been widely identified in different RNA molecules. RNA methylation modifications have various kinds, such as 5-methylcytosine (m5C). However, for individual methylation sites, their functions still remain to be elucidated. Testing of all methylation sites relies heavily on high-throughput sequencing technology, which is expensive and labor consuming. Thus, computational prediction approaches could serve as a substitute. In this study, multiple machine learning models were used to predict possible RNA m5C sites on the basis of mRNA sequences in human and mouse. Each site was represented by several features derived from k -mers of an RNA subsequence containing such site as center. The powerful max-relevance and min-redundancy (mRMR) feature selection method was employed to analyse these features. The outcome feature list was fed into incremental feature selection method, incorporating four classification algorithms, to build efficient models. Furthermore, the sites related to features used in the models were also investigated. [ABSTRACT FROM AUTHOR]

COVID-19, a severe respiratory disease caused by a new type of coronavirus SARS-CoV-2, has been spreading all over the world. Patients infected with SARS-CoV-2 may have no pathogenic symptoms, i.e., presymptomatic patients and asymptomatic patients. Both patients could further spread the virus to other susceptible people, thereby making the control of COVID-19 difficult. The two major challenges for COVID-19 diagnosis at present are as follows: (1) patients could share similar symptoms with other respiratory infections, and (2) patients may not have any symptoms but could still spread the virus. Therefore, new biomarkers at different omics levels are required for the large-scale screening and diagnosis of COVID-19. Although some initial analyses could identify a group of candidate gene biomarkers for COVID-19, the previous work still could not identify biomarkers capable for clinical use in COVID-19, which requires disease-specific diagnosis compared with other multiple infectious diseases. As an extension of the previous study, optimized machine learning models were applied in the present study to identify some specific qualitative host biomarkers associated with COVID-19 infection on the basis of a publicly released transcriptomic dataset, which included healthy controls and patients with bacterial infection, influenza, COVID-19, and other kinds of coronavirus. This dataset was first analysed by Boruta, Max-Relevance and Min-Redundancy feature selection methods one by one, resulting in a feature list. This list was fed into the incremental feature selection method, incorporating one of the classification algorithms to extract essential biomarkers and build efficient classifiers and classification rules. The capacity of these findings to distinguish COVID-19 with other similar respiratory infectious diseases at the transcriptomic level was also validated, which may improve the efficacy and accuracy of COVID-19 diagnosis. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a severe chronic pathogenic inflammatory abnormality that damages small joints. Comprehensive diagnosis and treatment procedures for RA have been established because of its severe symptoms and relatively high morbidity. Medication and surgery are the two major therapeutic approaches. Infliximab (IFX) is a novel biological agent applied for the treatment of RA. IFX improves physical functions and benefits the achievement of clinical remission even under discontinuous medication. However, not all patients react to IFX, and distinguishing IFX-sensitive and IFX-resistant patients is quite difficult. Thus, how to predict the therapeutic effects of IFX on patients with RA is one of the urgent translational medicine problems in the clinical treatment of RA. In this study, we present a novel computational method for the identification of the applicable and substantial blood gene signatures of IFX sensitivity by liquid biopsy, which may assist in the establishment of a clinical drug sensitivity test standard for RA and contribute to the revelation of unique IFX-associated pharmacological mechanisms. [ABSTRACT FROM AUTHOR]

The immune system is a complicated defensive system that comprises multiple functional cells and molecules acting against endogenous and exogenous pathogenic factors. Identifying immune cell subtypes and recognizing their unique immunological functions are difficult because of the complicated cellular components and immunological functions of the immune system. With the development of transcriptomics and high-throughput sequencing, the gene expression profiling of immune cells can provide a new strategy to explore the immune cell subtyping. On the basis of the new profiling data of mouse immune cell gene expression from the Immunological Genome Project (ImmGen), a novel computational pipeline was applied to identify different immune cell subtypes, including αβ T cells, B cells, γδ T cells, and innate lymphocytes. First, the profiling data was analyzed by a powerful feature selection method, Monte-Carlo Feature Selection, resulting in a feature list and some informative features. For the list, the two-stage incremental feature selection method, incorporating random forest as the classification algorithm, was applied to extract essential gene signatures and build an efficient classifier. On the other hand, a rule learning scheme was applied on the informative features to construct quantitative expression rules. A group of gene signatures was found as qualitatively related to the biological processes of four immune cell subtypes. The quantitative expression rules can efficiently cluster immune cells. This work provides a novel computational tool for immune cell quantitative subtyping and biomarker recognition. [ABSTRACT FROM AUTHOR]

Coronaviruses are specific crown-shaped viruses that were first identified in the 1960s, and three typical examples of the most recent coronavirus disease outbreaks include severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19. Particularly, COVID-19 is currently causing a worldwide pandemic, threatening the health of human beings globally. The identification of viral pathogenic mechanisms is important for further developing effective drugs and targeted clinical treatment methods. The delayed revelation of viral infectious mechanisms is currently one of the technical obstacles in the prevention and treatment of infectious diseases. In this study, we proposed a random walk model to identify the potential pathological mechanisms of COVID-19 on a virus–human protein interaction network, and we effectively identified a group of proteins that have already been determined to be potentially important for COVID-19 infection and for similar SARS infections, which help further developing drugs and targeted therapeutic methods against COVID-19. Moreover, we constructed a standard computational workflow for predicting the pathological biomarkers and related pharmacological targets of infectious diseases. [ABSTRACT FROM AUTHOR]

Among various risk factors for the initiation and progression of cancer, alternative polyadenylation (APA) is a remarkable endogenous contributor that directly triggers the malignant phenotype of cancer cells. APA affects biological processes at a transcriptional level in various ways. As such, APA can be involved in tumorigenesis through gene expression, protein subcellular localization, or transcription splicing pattern. The APA sites and status of different cancer types may have diverse modification patterns and regulatory mechanisms on transcripts. Potential APA sites were screened by applying several machine learning algorithms on a TCGA-APA dataset. First, a powerful feature selection method, minimum redundancy maximum relevancy, was applied on the dataset, resulting in a feature list. Then, the feature list was fed into the incremental feature selection, which incorporated the support vector machine as the classification algorithm, to extract key APA features and build a classifier. The classifier can classify cancer patients into cancer types with perfect performance. The key APA-modified genes had a potential prognosis ability because of their significant power in the survival analysis of TCGA pan-cancer data. [ABSTRACT FROM AUTHOR]

Protein–protein interaction (PPI) plays an extremely remarkable role in the growth, reproduction, and metabolism of all lives. A thorough investigation of PPI can uncover the mechanism of how proteins express their functions. In this study, we used gene ontology (GO) terms and biological pathways to study an extended version of PPI (protein–protein functional associations) and subsequently identify some essential GO terms and pathways that can indicate the difference between two proteins with and without functional associations. The protein–protein functional associations validated by experiments were retrieved from STRING, a well-known database on collected associations between proteins from multiple sources, and they were termed as positive samples. The negative samples were constructed by randomly pairing two proteins. Each sample was represented by several features based on GO and KEGG pathway information of two proteins. Then, the mutual information was adopted to evaluate the importance of all features and some important ones could be accessed, from which a number of essential GO terms or KEGG pathways were identified. The final analysis of some important GO terms and one KEGG pathway can partly uncover the difference between proteins with and without functional associations. [ABSTRACT FROM AUTHOR]

Background. Accumulating evidence has demonstrated the pivotal role of long noncoding RNAs (lncRNAs) in competing endogenous RNA (ceRNA) networks for predicting survival and evaluating prognosis in cancer patients. However, the pathogenesis of head and neck squamous cell carcinoma (HNSCC) remains unclear, and prognostic biomarkers for HNSCC are still lacking. Methods. A total of 546 RNA sequencing profiles of HNSCC patients with clinical outcome data were obtained from the Cancer Genome Atlas (TCGA) database, providing a large sample of RNA sequencing data. From these, 71 Long noncoding RNAs lncRNAs, 8 microRNAs (miRNAs), and 16 messenger RNAs (mRNAs) were identified to construct a HNSCC-specific ceRNA network (fold change >2, P < 0.05). Univariate and multivariate Cox proportional regression models were used to assess independent indicators of prognosis. Then the expression of lncRNAs harboring prognostic value was validated in human HNSCC cell lines and tumor samples from our cohort and another two datasets from GEO (Gene Expression Omnibus) databases. Results. As a result, a 3-mRNA signature and 6-lncRNA signature were identified. The six-lncRNA signature exhibited the highest prognostic value. Notably, in the six lncRNAs, HOTTIP showed the greatest prognostic value and was significantly correlated with clinical stage and histological grade of HNSCC patients. Furthermore, it was proved that HOTTIP was upregulated in HNSCC cell lines and cancerous tissues compared with corresponding normal cell lines and normal tissues. Functional assessment analysis revealed that HOTTIP might play a key role in the oncogenesis and progression of HNSCC. Conclusion. The present study deepened our understanding of the ceRNA-related regulatory mechanism in the pathogenesis of HNSCC and identified candidate prognostic biomarkers for clinical outcome prediction in HNSCC. HOTTIP may function as a key candidate biomarker in HNSCC and serve as a prognostic marker for HNSCC patients. [ABSTRACT FROM AUTHOR]

Identification of disease genes is a hot topic in biomedicine and genomics. However, it is a challenging problem because of the complexity of diseases. Inflammatory bowel disease (IBD) is an idiopathic disease caused by a dysregulated immune response to host intestinal microflora. It has been proven to be associated with the development of intestinal malignancies. Although the specific pathological characteristics and genetic background of IBD have been partially revealed, it is still an overdetermined disease and the blueprint of all genetic variants still needs to be improved. In this study, a novel computational method was built to identify genes related to IBD. Samples from two subtypes of IBD (ulcerative colitis and Crohn’s disease) and normal samples were employed. By analyzing the gene expression profiles of these samples using minimum redundancy maximum relevance and incremental feature selection, 21 genes were obtained that could effectively distinguish samples from the two subtypes of IBD and the normal samples. Then, the shortest-path approach was used to search for an additional 20 genes in a large network constructed using protein-protein interactions based on the above-mentioned 21 genes. Analyses of the 41 genes obtained indicate that they are closely associated with this disease. [ABSTRACT FROM AUTHOR]

The regulation of transcriptome expression level is a complex process involving multiple-level interactions among molecules such as protein coding RNA (mRNA), long noncoding RNA (lncRNA), and microRNA (miRNA), which are essential for the transcriptome stability and maintenance and regulation of body homeostasis. The availability of multilevel expression data enables a comprehensive view of the regulatory network. In this study, we analyzed the coding and noncoding gene expression profiles of 301 patients with uterine corpus endometrial carcinoma (UCEC). A new method was proposed to construct a genome-wide integrative network based on variance inflation factor (VIF) regression method. The cross-regulation relations of mRNA, lncRNA, and miRNA were then selected based on clique-searching algorithm from the network, when any two molecules of the three were shown as interacting according to the integrative network. Such relation, which we call the mRNA-lncRNA-miRNA triplet, demonstrated the complexity in transcriptome regulation process. Finally, six UCEC-related triplets were selected in which the mRNA participates in endometrial carcinoma pathway, such as CDH1 and TP53. The multi-type RNAs are proved to be cross-regulated as to each of the six triplets according to literature. All the triplets demonstrated the association with the initiation and progression of UCEC. Our method provides a comprehensive strategy for the investigation of transcriptome regulation mechanism. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a serious disease that results in more than thirty thousand deaths around the world per year. To design effective treatments, many investigators have devoted themselves to the study of biological processes and mechanisms underlying this disease. However, it is far from complete. In this study, we tried to extract important gene ontology (GO) terms and KEGG pathways for pancreatic cancer by adopting some existing computational methods. Genes that have been validated to be related to pancreatic cancer and have not been validated were represented by features derived from GO terms and KEGG pathways using the enrichment theory. A popular feature selection method, minimum redundancy maximum relevance, was employed to analyze these features and extract important GO terms and KEGG pathways. An extensive analysis of the obtained GO terms and KEGG pathways was provided to confirm the correlations between them and pancreatic cancer. [ABSTRACT FROM AUTHOR]

The development of biochemistry and molecular biology has revealed an increasingly important role of compounds in several biological processes. Like the aptamer-protein interaction, aptamer-compound interaction attracts increasing attention. However, it is time-consuming to select proper aptamers against compounds using traditional methods, such as exponential enrichment. Thus, there is an urgent need to design effective computational methods for searching effective aptamers against compounds. This study attempted to extract important features for aptamer-compound interactions using feature selection methods, such as Maximum Relevance Minimum Redundancy, as well as incremental feature selection. Each aptamer-compound pair was represented by properties derived from the aptamer and compound, including frequencies of single nucleotides and dinucleotides for the aptamer, as well as the constitutional, electrostatic, quantum-chemical, and space conformational descriptors of the compounds. As a result, some important features were obtained. To confirm the importance of the obtained features, we further discussed the associations between them and aptamer-compound interactions. Simultaneously, an optimal prediction model based on the nearest neighbor algorithm was built to identify aptamer-compound interactions, which has the potential to be a useful tool for the identification of novel aptamer-compound interactions. The program is available upon the request. [ABSTRACT FROM AUTHOR]

Discovering potential indications of novel or approved drugs is a key step in drug development. Previous computational approaches could be categorized into disease-centric and drug-centric based on the starting point of the issues or small-scaled application and large-scale application according to the diversity of the datasets. Here, a classifier has been constructed to predict the indications of a drug based on the assumption that interactive/associated drugs or drugs with similar structures are more likely to target the same diseases using a large drug indication dataset. To examine the classifier, it was conducted on a dataset with 1,573 drugs retrieved from Comprehensive Medicinal Chemistry database for five times, evaluated by 5-fold cross-validation, yielding five 1st order prediction accuracies that were all approximately 51.48%. Meanwhile, the model yielded an accuracy rate of 50.00% for the 1st order prediction by independent test on a dataset with 32 other drugs in which drug repositioning has been confirmed. Interestingly, some clinically repurposed drug indications that were not included in the datasets are successfully identified by our method. These results suggest that our method may become a useful tool to associate novel molecules with new indications or alternative indications with existing drugs. [ABSTRACT FROM AUTHOR]

Purpose. Recent studies suggest that tinnitus may be due in part to aberrant callosal structure and interhemispheric interaction. To explore this hypothesis we use a novel method, voxel-mirrored homotopic connectivity (VMHC), to examine the resting-state interhemispheric functional connectivity and its relationships with clinical characteristics in chronic tinnitus patients. Materials and Methods. Twenty-eight chronic tinnitus patients with normal hearing thresholds and 30 age-, sex-, education-, and hearing threshold-matched healthy controls were included in this study and underwent the resting-state fMRI scanning. We computed the VMHC to analyze the interhemispheric functional coordination between homotopic points of the brain in both groups. Results. Compared to the controls, tinnitus patients showed significantly increased VMHC in the middle temporal gyrus, middle frontal gyrus, and superior occipital gyrus. In tinnitus patients, a positive correlation was found between tinnitus duration and VMHC of the uncus. Moreover, correlations between VMHC changes and tinnitus distress were observed in the transverse temporal gyrus, superior temporal pole, precentral gyrus, and calcarine cortex. Conclusions. These results show altered interhemispheric functional connectivity linked with specific tinnitus characteristics in chronic tinnitus patients, which may be implicated in the neuropathophysiology of tinnitus. [ABSTRACT FROM AUTHOR]

A drug side effect is an undesirable effect which occurs in addition to the intended therapeutic effect of the drug. The unexpected side effects that many patients suffer from are the major causes of large-scale drug withdrawal. To address the problem, it is highly demanded by pharmaceutical industries to develop computational methods for predicting the side effects of drugs. In this study, a novel computational method was developed to predict the side effects of drug compounds by hybridizing the chemical-chemical and protein-chemical interactions. Compared to most of the previous works, our method can rank the potential side effects for any query drug according to their predicted level of risk. A training dataset and test datasets were constructed from the benchmark dataset that contains 835 drug compounds to evaluate the method. By ajackknife test on the training dataset, the 1st order prediction accuracy was 86.30%, while it was 89.16% on the test dataset. It is expected that the new method may become a useful tool for drug design, and that the findings obtained by hybridizing various interactions in a network system may provide useful insights for conducting in-depth pharmacological research as well, particularly at the level of systems biomedicine. [ABSTRACT FROM AUTHOR]

With a large number of disordered proteins and their important functions discovered, it is highly desired to develop effective methods to computationally predict protein disordered regions. In this study, based on Random Forest (RF), Maximum Relevancy Minimum Redundancy (mRMR), and Incremental Feature Selection (IFS), we developed a new method to predict disordered regions in proteins. The mRMR criterion was used to rank the importance of all candidate features. Finally, top 128 features were selected from the ranked feature list to build the optimal model, including 92 Position Specific Scoring Matrix (PSSM) conservation score features and 36 secondary structure features. As a result, Matthews correlation coefficient (MCC) of 0.3895 was achieved on the training set by 10-fold cross-validation. On the basis of predicting results for each query sequence by using the method, we used the scanning and modification strategy to improve the performance. The accuracy (ACC) and MCC were increased by 4% and almost 0.2%, respectively, compared with other three popular predictors: DISOPRED, DISOclust, and OnD-CRF. The selected features may shed some light on the understanding of the formation mechanism of disordered structures, providing guidelines for experimental validation. [ABSTRACT FROM AUTHOR]

This study attempted to find novel age-related macular degeneration (AMD) related genes based on 36 known AMD genes. The well-known shortest path algorithm, Dijkstra's algorithm, was applied to find the shortest path connecting each pair of known AMD related genes in protein-protein interaction (PPI) network. The genes occurring in any shortest path were considered as candidate AMD related genes. As a result, 125 novel AMD genes were predicted. The further analysis based on betweenness and permutation test indicates that there are 10 genes involved in the formation or development of AMD and may be the actual AMD related genes with high probability. We hope that this contribution would promote the study of age-related macular degeneration and discovery of novel effective treatments. [ABSTRACT FROM AUTHOR]