Predicting Mycobacterium tuberculosis Complex Clades Using Knowledge-Based Bayesian Networks

We develop a novel approach for incorporating expert rules into Bayesian networks for classification of Mycobacterium tuberculosis complex (MTBC) clades. The proposed knowledge-based Bayesian network (KBBN) treats sets of expert rules as prior distributions on the classes. Unlike prior knowledge-based support vector machine approaches which require rules expressed as polyhedral sets, KBBN directly incorporates the rules without any modification. KBBN uses data to refine rule-based classifiers when the rule set is incomplete or ambiguous. We develop a predictive KBBN model for 69 MTBC clades found in the SITVIT international collection. We validate the approach using two testbeds that model knowledge of the MTBC obtained from two different experts and large DNA fingerprint databases to predict MTBC genetic clades and sublineages. These models represent strains of MTBC using high-throughput biomarkers called spacer oligonucleotide types (spoligotypes), since these are routinely gathered from MTBC isolates of tuberculosis (TB) patients. Results show that incorporating rules into problems can drastically increase classification accuracy if data alone are insufficient. The SITVIT KBBN is publicly available for use on the World Wide Web

Comprehensive analysis of the candidate genes CCL2, CCR2, and TLR4 in age-related macular degeneration

PURPOSE. To determine whether variants in the candidate genes TLR4, CCL2, and CCR2 are associated with age-related macular degeneration (AMD). METHODS. This study was performed in two independent Caucasian populations that included 357 cases and 173 controls from the Netherlands and 368 cases and 368 controls from the United States. Exon 4 of the TLR4 gene and the promoter, all exons, and flanking intronic regions of the CCL2 and CCR2 genes were analyzed in the Dutch study and common variants were validated in the U.S. study. Quantitative (q)PCR reactions were performed to evaluate expression of these genes in laser-dissected retinal pigment epithelium from 13 donor AMD and 13 control eyes. RESULTS. Analysis of single nucleotide polymorphisms (SNPs) in the TLR4 gene did not show a significant association between D299G or T399I and AMD, nor did haplotypes containing these variants. Univariate analyses of the SNPs in CCL2 and CCR2 did not demonstrate an association with AMD. For CCR2, haplotype frequencies were not significantly different between cases and controls. For CCL2, one haplotype containing the minor allele of C35C was significantly associated with AM

Demographic Details for All Genotyped Patients included in the Study.

<p>¹Susceptible to rifampicin and isoniazid.</p><p>²Average Socio Economic Status (SES) of the city block in which the patient lived.</p><p>^†Phenotypic data was not available for <1% of samples.</p><p>Demographic Details for All Genotyped Patients included in the Study.</p

A minimum spanning tree of all study genotypes.

<p>Each coloured node is a different patient; green drug sensitive, red multidrug resistant, pink mono-resistant, light blue unknown. Patients grouped closely together have identical MIRU types and spoligotypes. A linking line between nodes denotes a change in Manhattan distance equal to 1.</p

A UPGMA phylogeny of all study strains.

<p>Beijing strains coloured red, X clade coloured yellow, Haarlem clade blue, T clade purple and Latin American Mediterranean green. Strains belonging to other families and strains that could not be subscribed a family as they were too distant from strains in the MIRU-VNTRplus database are shown in grey.</p