Brian R King, Maurice Aburdene, Alex Thompson, Zach Warres
{"title":"Application of discrete Fourier inter-coefficient difference for assessing genetic sequence similarity.","authors":"Brian R King, Maurice Aburdene, Alex Thompson, Zach Warres","doi":"10.1186/1687-4153-2014-8","DOIUrl":"https://doi.org/10.1186/1687-4153-2014-8","url":null,"abstract":"<p><p>Digital signal processing (DSP) techniques for biological sequence analysis continue to grow in popularity due to the inherent digital nature of these sequences. DSP methods have demonstrated early success for detection of coding regions in a gene. Recently, these methods are being used to establish DNA gene similarity. We present the inter-coefficient difference (ICD) transformation, a novel extension of the discrete Fourier transformation, which can be applied to any DNA sequence. The ICD method is a mathematical, alignment-free DNA comparison method that generates a genetic signature for any DNA sequence that is used to generate relative measures of similarity among DNA sequences. We demonstrate our method on a set of insulin genes obtained from an evolutionarily wide range of species, and on a set of avian influenza viral sequences, which represents a set of highly similar sequences. We compare phylogenetic trees generated using our technique against trees generated using traditional alignment techniques for similarity and demonstrate that the ICD method produces a highly accurate tree without requiring an alignment prior to establishing sequence similarity. </p>","PeriodicalId":72957,"journal":{"name":"EURASIP journal on bioinformatics & systems biology","volume":"2014 1","pages":"8"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1687-4153-2014-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32476629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hongjia Ouyang, Jie Fang, Liangzhong Shen, Edward R Dougherty, Wenbin Liu
{"title":"Learning restricted Boolean network model by time-series data.","authors":"Hongjia Ouyang, Jie Fang, Liangzhong Shen, Edward R Dougherty, Wenbin Liu","doi":"10.1186/s13637-014-0010-5","DOIUrl":"10.1186/s13637-014-0010-5","url":null,"abstract":"<p><p>Restricted Boolean networks are simplified Boolean networks that are required for either negative or positive regulations between genes. Higa et al. (BMC Proc 5:S5, 2011) proposed a three-rule algorithm to infer a restricted Boolean network from time-series data. However, the algorithm suffers from a major drawback, namely, it is very sensitive to noise. In this paper, we systematically analyze the regulatory relationships between genes based on the state switch of the target gene and propose an algorithm with which restricted Boolean networks may be inferred from time-series data. We compare the proposed algorithm with the three-rule algorithm and the best-fit algorithm based on both synthetic networks and a well-studied budding yeast cell cycle network. The performance of the algorithms is evaluated by three distance metrics: the normalized-edge Hamming distance [Formula: see text], the normalized Hamming distance of state transition [Formula: see text], and the steady-state distribution distance μ (ssd). Results show that the proposed algorithm outperforms the others according to both [Formula: see text] and [Formula: see text], whereas its performance according to μ (ssd) is intermediate between best-fit and the three-rule algorithms. Thus, our new algorithm is more appropriate for inferring interactions between genes from time-series data. </p>","PeriodicalId":72957,"journal":{"name":"EURASIP journal on bioinformatics & systems biology","volume":"2014 1","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4107581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32561156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gene regulatory network inference by point-based Gaussian approximation filters incorporating the prior information.","authors":"Bin Jia, Xiaodong Wang","doi":"10.1186/1687-4153-2013-16","DOIUrl":"https://doi.org/10.1186/1687-4153-2013-16","url":null,"abstract":"<p><p>: The extended Kalman filter (EKF) has been applied to inferring gene regulatory networks. However, it is well known that the EKF becomes less accurate when the system exhibits high nonlinearity. In addition, certain prior information about the gene regulatory network exists in practice, and no systematic approach has been developed to incorporate such prior information into the Kalman-type filter for inferring the structure of the gene regulatory network. In this paper, an inference framework based on point-based Gaussian approximation filters that can exploit the prior information is developed to solve the gene regulatory network inference problem. Different point-based Gaussian approximation filters, including the unscented Kalman filter (UKF), the third-degree cubature Kalman filter (CKF3), and the fifth-degree cubature Kalman filter (CKF5) are employed. Several types of network prior information, including the existing network structure information, sparsity assumption, and the range constraint of parameters, are considered, and the corresponding filters incorporating the prior information are developed. Experiments on a synthetic network of eight genes and the yeast protein synthesis network of five genes are carried out to demonstrate the performance of the proposed framework. The results show that the proposed methods provide more accurate inference results than existing methods, such as the EKF and the traditional UKF. </p>","PeriodicalId":72957,"journal":{"name":"EURASIP journal on bioinformatics & systems biology","volume":"2013 1","pages":"16"},"PeriodicalIF":0.0,"publicationDate":"2013-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1687-4153-2013-16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31957258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"On the impoverishment of scientific education.","authors":"Edward R Dougherty","doi":"10.1186/1687-4153-2013-15","DOIUrl":"https://doi.org/10.1186/1687-4153-2013-15","url":null,"abstract":"<p><p>Hannah Arendt, one of the foremost political philosophers of the twentieth century, has argued that it is the responsibility of educators not to leave children in their own world but instead to bring them into the adult world so that, as adults, they can carry civilization forward to whatever challenges it will face by bringing to bear the learning of the past. In the same collection of essays, she discusses the recognition by modern science that Nature is inconceivable in terms of ordinary human conceptual categories - as she writes, 'unthinkable in terms of pure reason'. Together, these views on scientific education lead to an educational process that transforms children into adults, with a scientific adult being one who has the ability to conceptualize scientific systems independent of ordinary physical intuition. This article begins with Arendt's basic educational and scientific points and develops from them a critique of current scientific education in conjunction with an appeal to educate young scientists in a manner that allows them to fulfill their potential 'on the shoulders of giants'. While the article takes a general philosophical perspective, its specifics tend to be directed at biomedical education, in particular, how such education pertains to translational science. </p>","PeriodicalId":72957,"journal":{"name":"EURASIP journal on bioinformatics & systems biology","volume":"2013 1","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2013-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1687-4153-2013-15","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31851697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identification of genomic functional hotspots with copy number alteration in liver cancer.","authors":"Tzu-Hung Hsiao, Hung-I Harry Chen, Stephanie Roessler, Xin Wei Wang, Yidong Chen","doi":"10.1186/1687-4153-2013-14","DOIUrl":"https://doi.org/10.1186/1687-4153-2013-14","url":null,"abstract":"<p><p>Copy number alterations (CNAs) can be observed in most of cancer patients. Several oncogenes and tumor suppressor genes with CNAs have been identified in different kinds of tumor. However, the systematic survey of CNA-affected functions is still lack. By employing systems biology approaches, instead of examining individual genes, we directly identified the functional hotspots on human genome. A total of 838 hotspots on human genome with 540 enriched Gene Ontology functions were identified. Seventy-six aCGH array data of hepatocellular carcinoma (HCC) tumors were employed in this study. A total of 150 regions which putatively affected by CNAs and the encoded functions were identified. Our results indicate that two immune related hotspots had copy number alterations in most of patients. In addition, our data implied that these immune-related regions might be involved in HCC oncogenesis. Also, we identified 39 hotspots of which copy number status were associated with patient survival. Our data implied that copy number alterations of the regions may contribute in the dysregulation of the encoded functions. These results further demonstrated that our method enables researchers to survey biological functions of CNAs and to construct regulation hypothesis at pathway and functional levels. </p>","PeriodicalId":72957,"journal":{"name":"EURASIP journal on bioinformatics & systems biology","volume":" ","pages":"14"},"PeriodicalIF":0.0,"publicationDate":"2013-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1687-4153-2013-14","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40266587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elizabeth M Jennings, Jeffrey S Morris, Raymond J Carroll, Ganiraju C Manyam, Veerabhadran Baladandayuthapani
{"title":"Bayesian methods for expression-based integration of various types of genomics data.","authors":"Elizabeth M Jennings, Jeffrey S Morris, Raymond J Carroll, Ganiraju C Manyam, Veerabhadran Baladandayuthapani","doi":"10.1186/1687-4153-2013-13","DOIUrl":"10.1186/1687-4153-2013-13","url":null,"abstract":"<p><p>: We propose methods to integrate data across several genomic platforms using a hierarchical Bayesian analysis framework that incorporates the biological relationships among the platforms to identify genes whose expression is related to clinical outcomes in cancer. This integrated approach combines information across all platforms, leading to increased statistical power in finding these predictive genes, and further provides mechanistic information about the manner in which the gene affects the outcome. We demonstrate the advantages of the shrinkage estimation used by this approach through a simulation, and finally, we apply our method to a Glioblastoma Multiforme dataset and identify several genes potentially associated with the patients' survival. We find 12 positive prognostic markers associated with nine genes and 13 negative prognostic markers associated with nine genes. </p>","PeriodicalId":72957,"journal":{"name":"EURASIP journal on bioinformatics & systems biology","volume":"2013 1","pages":"13"},"PeriodicalIF":0.0,"publicationDate":"2013-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1687-4153-2013-13","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31748335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Feature ranking based on synergy networks to identify prognostic markers in DPT-1.","authors":"Amin Ahmadi Adl, Xiaoning Qian, Ping Xu, Kendra Vehik, Jeffrey P Krischer","doi":"10.1186/1687-4153-2013-12","DOIUrl":"https://doi.org/10.1186/1687-4153-2013-12","url":null,"abstract":"<p><p>: Interaction among different risk factors plays an important role in the development and progress of complex disease, such as diabetes. However, traditional epidemiological methods often focus on analyzing individual or a few 'essential' risk factors, hopefully to obtain some insights into the etiology of complex disease. In this paper, we propose a systematic framework for risk factor analysis based on a synergy network, which enables better identification of potential risk factors that may serve as prognostic markers for complex disease. A spectral approximate algorithm is derived to solve this network optimization problem, which leads to a new network-based feature ranking method that improves the traditional feature ranking by taking into account the pairwise synergistic interactions among risk factors in addition to their individual predictive power. We first evaluate the performance of our method based on simulated datasets, and then, we use our method to study immunologic and metabolic indices based on the Diabetes Prevention Trial-Type 1 (DPT-1) study that may provide prognostic and diagnostic information regarding the development of type 1 diabetes. The performance comparison based on both simulated and DPT-1 datasets demonstrates that our network-based ranking method provides prognostic markers with higher predictive power than traditional analysis based on individual factors. </p>","PeriodicalId":72957,"journal":{"name":"EURASIP journal on bioinformatics & systems biology","volume":"2013 1","pages":"12"},"PeriodicalIF":0.0,"publicationDate":"2013-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1687-4153-2013-12","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31745527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inferring Boolean network states from partial information.","authors":"Guy Karlebach","doi":"10.1186/1687-4153-2013-11","DOIUrl":"10.1186/1687-4153-2013-11","url":null,"abstract":"<p><p>Networks of molecular interactions regulate key processes in living cells. Therefore, understanding their functionality is a high priority in advancing biological knowledge. Boolean networks are often used to describe cellular networks mathematically and are fitted to experimental datasets. The fitting often results in ambiguities since the interpretation of the measurements is not straightforward and since the data contain noise. In order to facilitate a more reliable mapping between datasets and Boolean networks, we develop an algorithm that infers network trajectories from a dataset distorted by noise. We analyze our algorithm theoretically and demonstrate its accuracy using simulation and microarray expression data. </p>","PeriodicalId":72957,"journal":{"name":"EURASIP journal on bioinformatics & systems biology","volume":"2013 1","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2013-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31709255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Scientific knowledge is possible with small-sample classification.","authors":"Edward R Dougherty, Lori A Dalton","doi":"10.1186/1687-4153-2013-10","DOIUrl":"https://doi.org/10.1186/1687-4153-2013-10","url":null,"abstract":"<p><p>: A typical small-sample biomarker classification paper discriminates between types of pathology based on, say, 30,000 genes and a small labeled sample of less than 100 points. Some classification rule is used to design the classifier from this data, but we are given no good reason or conditions under which this algorithm should perform well. An error estimation rule is used to estimate the classification error on the population using the same data, but once again we are given no good reason or conditions under which this error estimator should produce a good estimate, and thus we do not know how well the classifier should be expected to perform. In fact, virtually, in all such papers the error estimate is expected to be highly inaccurate. In short, we are given no justification for any claims.Given the ubiquity of vacuous small-sample classification papers in the literature, one could easily conclude that scientific knowledge is impossible in small-sample settings. It is not that thousands of papers overtly claim that scientific knowledge is impossible in regard to their content; rather, it is that they utilize methods that preclude scientific knowledge. In this paper, we argue to the contrary that scientific knowledge in small-sample classification is possible provided there is sufficient prior knowledge. A natural way to proceed, discussed herein, is via a paradigm for pattern recognition in which we incorporate prior knowledge in the whole classification procedure (classifier design and error estimation), optimize each step of the procedure given available information, and obtain theoretical measures of performance for both classifiers and error estimators, the latter being the critical epistemological issue. In sum, we can achieve scientific validation for a proposed small-sample classifier and its error estimate. </p>","PeriodicalId":72957,"journal":{"name":"EURASIP journal on bioinformatics & systems biology","volume":"2013 1","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2013-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1687-4153-2013-10","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31667997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sanvesh Srivastava, Wenyi Wang, Ganiraju Manyam, Carlos Ordonez, Veerabhadran Baladandayuthapani
{"title":"Integrating multi-platform genomic data using hierarchical Bayesian relevance vector machines.","authors":"Sanvesh Srivastava, Wenyi Wang, Ganiraju Manyam, Carlos Ordonez, Veerabhadran Baladandayuthapani","doi":"10.1186/1687-4153-2013-9","DOIUrl":"https://doi.org/10.1186/1687-4153-2013-9","url":null,"abstract":"<p><strong>Background: </strong>Recent advances in genome technologies and the subsequent collection of genomic information at various molecular resolutions hold promise to accelerate the discovery of new therapeutic targets. A critical step in achieving these goals is to develop efficient clinical prediction models that integrate these diverse sources of high-throughput data. This step is challenging due to the presence of high-dimensionality and complex interactions in the data. For predicting relevant clinical outcomes, we propose a flexible statistical machine learning approach that acknowledges and models the interaction between platform-specific measurements through nonlinear kernel machines and borrows information within and between platforms through a hierarchical Bayesian framework. Our model has parameters with direct interpretations in terms of the effects of platforms and data interactions within and across platforms. The parameter estimation algorithm in our model uses a computationally efficient variational Bayes approach that scales well to large high-throughput datasets.</p><p><strong>Results: </strong>We apply our methods of integrating gene/mRNA expression and microRNA profiles for predicting patient survival times to The Cancer Genome Atlas (TCGA) based glioblastoma multiforme (GBM) dataset. In terms of prediction accuracy, we show that our non-linear and interaction-based integrative methods perform better than linear alternatives and non-integrative methods that do not account for interactions between the platforms. We also find several prognostic mRNAs and microRNAs that are related to tumor invasion and are known to drive tumor metastasis and severe inflammatory response in GBM. In addition, our analysis reveals several interesting mRNA and microRNA interactions that have known implications in the etiology of GBM.</p><p><strong>Conclusions: </strong>Our approach gains its flexibility and power by modeling the non-linear interaction structures between and within the platforms. Our framework is a useful tool for biomedical researchers, since clinical prediction using multi-platform genomic information is an important step towards personalized treatment of many cancers. We have a freely available software at: http://odin.mdacc.tmc.edu/~vbaladan.</p>","PeriodicalId":72957,"journal":{"name":"EURASIP journal on bioinformatics & systems biology","volume":"2013 1","pages":"9"},"PeriodicalIF":0.0,"publicationDate":"2013-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1687-4153-2013-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31541607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}