High performance subgraph mining in molecular compounds

Structured data represented in the form of graphs arises in several fields of the science and the growing amount of available data makes distributed graph mining techniques particularly relevant. In this paper, we present a distributed approach to the frequent subgraph mining problem to discover interesting patterns in molecular compounds. The problem is characterized by a highly irregular search tree, whereby no reliable workload prediction is available. We describe the three main aspects of the proposed distributed algorithm, namely a dynamic partitioning of the search space, a distribution process based on a peer-to-peer communication framework, and a novel receiver-initiated, load balancing algorithm. The effectiveness of the distributed method has been evaluated on the well-known National Cancer Institute’s HIV-screening dataset, where the approach attains close-to linear speedup in a network of workstations

Mining Relational Paths in Integrated Biomedical Data

Much life science and biology research requires an understanding of complex relationships between biological entities (genes, compounds, pathways, diseases, and so on). There is a wealth of data on such relationships in publicly available datasets and publications, but these sources are overlapped and distributed so that finding pertinent relational data is increasingly difficult. Whilst most public datasets have associated tools for searching, there is a lack of searching methods that can cross data sources and that in particular search not only based on the biological entities themselves but also on the relationships between them. In this paper, we demonstrate how graph-theoretic algorithms for mining relational paths can be used together with a previous integrative data resource we developed called Chem2Bio2RDF to extract new biological insights about the relationships between such entities. In particular, we use these methods to investigate the genetic basis of side-effects of thiazolinedione drugs, and in particular make a hypothesis for the recently discovered cardiac side-effects of Rosiglitazone (Avandia) and a prediction for Pioglitazone which is backed up by recent clinical studies

Distributed mining of molecular fragments

In real world applications sequential algorithms of data mining and data exploration are often unsuitable for datasets with enormous size, high-dimensionality and complex data structure. Grid computing promises unprecedented opportunities for unlimited computing and storage resources. In this context there is the necessity to develop high performance distributed data mining algorithms. However, the computational complexity of the problem and the large amount of data to be explored often make the design of large scale applications particularly challenging. In this paper we present the first distributed formulation of a frequent subgraph mining algorithm for discriminative fragments of molecular compounds. Two distributed approaches have been developed and compared on the well known National Cancer Institute’s HIV-screening dataset. We present experimental results on a small-scale computing environment

Complex biomarker discovery in neuroimaging data: Finding a needle in a haystack

AbstractNeuropsychiatric disorders such as schizophrenia, bipolar disorder and Alzheimer's disease are major public health problems. However, despite decades of research, we currently have no validated prognostic or diagnostic tests that can be applied at an individual patient level. Many neuropsychiatric diseases are due to a combination of alterations that occur in a human brain rather than the result of localized lesions. While there is hope that newer imaging technologies such as functional and anatomic connectivity MRI or molecular imaging may offer breakthroughs, the single biomarkers that are discovered using these datasets are limited by their inability to capture the heterogeneity and complexity of most multifactorial brain disorders. Recently, complex biomarkers have been explored to address this limitation using neuroimaging data. In this manuscript we consider the nature of complex biomarkers being investigated in the recent literature and present techniques to find such biomarkers that have been developed in related areas of data mining, statistics, machine learning and bioinformatics

Effects of Environment, Genetics and Data Analysis Pitfalls in an Esophageal Cancer Genome-Wide Association Study

The development of new high-throughput genotyping technologies has allowed fast evaluation of single nucleotide polymorphisms (SNPs) on a genome-wide scale. Several recent genome-wide association studies employing these technologies suggest that panels of SNPs can be a useful tool for predicting cancer susceptibility and discovery of potentially important new disease loci.In the present paper we undertake a careful examination of the relative significance of genetics, environmental factors, and biases of the data analysis protocol that was used in a previously published genome-wide association study. That prior study reported a nearly perfect discrimination of esophageal cancer patients and healthy controls on the basis of only genetic information. On the other hand, our results strongly suggest that SNPs in this dataset are not statistically linked to the phenotype, while several environmental factors and especially family history of esophageal cancer (a proxy to both environmental and genetic factors) have only a modest association with the disease.The main component of the previously claimed strong discriminatory signal is due to several data analysis pitfalls that in combination led to the strongly optimistic results. Such pitfalls are preventable and should be avoided in future studies since they create misleading conclusions and generate many false leads for subsequent research

Visual Methods for Examining Support Vector Machine Results, with Applications to Gene Expression Data Analysis

Support vector machines (SVM) offer a theoretically well-founded approach to automated learning of pattern classifiers. They have been proven to give highly accurate results in complex classification problems, for example, gene expression analysis. The SVM algorithm is also quite intuitive with a few inputs to vary in the fitting process and several outputs that are interesting to study. For many data mining tasks (e.g., cancer prediction) finding classifiers with good predictive accuracy is important, but understanding the classifier is equally important. By studying the classifier outputs we may be able to produce a simpler classifier, learn which variables are the important discriminators between classes, and find the samples that are problematic to the classification. Visual methods for exploratory data analysis can help us to study the outputs and complement automated classification algorithms in data mining. We present the use of tour-based methods to plot aspects of the SVM classifier. This approach provides insights about the cluster structure in the data, the nature of boundaries between clusters, and problematic outliers. Furthermore, tours can be used to assess the variable importance. We show how visual methods can be used as a complement to cross-validation methods in order to find good SVM input parameters for a particular data set

Novel Implementation of Conditional Co-Regulation by Graph Theory to Derive Co-Expressed Genes from Microarray Data

BackgroundMost existing transcriptional databases like Comprehensive Systems-Biology Database (CSB.DB) and Arabidopsis Microarray Database and Analysis Toolbox (GENEVESTIGATOR) help to seek a shared biological role (similar pathways and biosynthetic cycles) based on correlation. These utilize conventional methods like Pearson correlation and Spearman rank correlation to calculate correlation among genes. However, not all are genes expressed in all the conditions and this leads to their exclusion in these transcriptional databases that consist of experiments performed in varied conditions. This leads to incomplete studies of co-regulation among groups of genes that might be linked to the same or related biosynthetic pathway. ResultsWe have implemented an alternate method based on graph theory that takes into consideration the biological assumption – conditional co-regulation is needed to mine a large transcriptional data bank and properties of microarray data. The algorithm calculates relationships among genes by converting discretized signals from the time series microarray data (AtGenExpress) to output strings. A \u27score\u27 is generated by using a similarity index against all the other genes by matching stored strings for any gene queried against our database. Taking carbohydrate metabolism as a test case, we observed that those genes known to be involved in similar functions and pathways generate a high \u27score\u27 with the queried gene. We were also able to recognize most of the randomly selected correlated pairs from Pearson correlation in CSB.DB and generate a higher number of relationships that might be biologically important. One advantage of our method over previously described approaches is that it includes all genes regardless of its expression values thereby highlighting important relationships absent in other contemporary databases. ConclusionBased on promising results, we understand that incorporating conditional co-regulation to study large expression data helps us identify novel relationships among genes. The other advantage of our approach is that mining expression data from various experiments, the genes that do not express in all the conditions or have low expression values are not excluded, thereby giving a better overall picture. This results in addressing known limitations of clustering methods in which genes that are expressed in only a subset of conditions are omitted. Based on further scope to extract information, ASIDB implementing above described approach has been initiated as a model database. ASIDB is available at http://www.asidb.co