On the Analysis of the Illumina 450k Array Data: Probes Ambiguously Mapped to the Human Genome

We pointed out that a substantial number of CpG probes on the Illumina 450K array could be mapped to multiple loci across the human genome. These CpGs need to be considered when interpreting results using this platform

Ancestry-informative markers for African Americans based on the Affymetrix Pan-African genotyping array

Genetic admixture has been utilized as a tool for identifying loci associated with complex traits and diseases in recently admixed populations such as African Americans. In particular, admixture mapping is an efficient approach to identifying genetic basis for those complex diseases with substantial racial or ethnic disparities. Though current advances in admixture mapping algorithms may utilize the entire panel of SNPs, providing ancestry-informative markers (AIMs) that can differentiate parental populations and estimate ancestry proportions in an admixed population may particularly benefit admixture mapping in studies of limited samples, help identify unsuitable individuals (e.g., through genotyping the most informative ancestry markers) before starting large genome-wide association studies (GWAS), or guide larger scale targeted deep re-sequencing for determining specific disease-causing variants. Defining panels of AIMs based on commercial, high-throughput genotyping platforms will facilitate the utilization of these platforms for simultaneous admixture mapping of complex traits and diseases, in addition to conventional GWAS. Here, we describe AIMs detected based on the Shannon Information Content (SIC) or Fst for African Americans with genome-wide coverage that were selected from ∼2.3 million single nucleotide polymorphisms (SNPs) covered by the Affymetrix Axiom Pan-African array, a newly developed genotyping platform optimized for individuals of African ancestry

A Local Genetic Algorithm for the Identification of Condition-Specific MicroRNA-Gene Modules

Transcription factor and microRNA are two types of key regulators of gene expression. Their regulatory mechanisms are highly complex. In this study, we propose a computational method to predict condition-specific regulatory modules that consist of microRNAs, transcription factors, and their commonly regulated genes. We used matched global expression profiles of mRNAs and microRNAs together with the predicted targets of transcription factors and microRNAs to construct an underlying regulatory network. Our method searches for highly scored modules from the network based on a two-step heuristic method that combines genetic and local search algorithms. Using two matched expression datasets, we demonstrate that our method can identify highly scored modules with statistical significance and biological relevance. The identified regulatory modules may provide useful insights on the mechanisms of transcription factors and microRNAs

Sanger Confirmation Is Required to Achieve Optimal Sensitivity and Specificity in Next-Generation Sequencing Panel Testing

Next-generation sequencing (NGS) has rapidly replaced Sanger sequencing as the method of choice for diagnostic gene-panel testing. For hereditary-cancer testing, the technical sensitivity and specificity of the assay are paramount as clinicians use results to make important clinical management and treatment decisions. There is significant debate within the diagnostics community regarding the necessity of confirming NGS variant calls by Sanger sequencing, considering that numerous laboratories report having 100% specificity from the NGS data alone. Here we report our results from 20,000 hereditary-cancer NGS panels spanning 47 genes, in which all 7845 nonpolymorphic variants were Sanger- sequenced. Of these, 98.7% were concordant between NGS and Sanger sequencing and 1.3% were identified as NGS false-positives, located mainly in complex genomic regions (A/T-rich regions, G/C-rich regions, homopolymer stretches, and pseudogene regions). Simulating a false-positive rate of zero by adjusting the variant-calling quality-score thresholds decreased the sensitivity of the assay from 100% to 97.8%, resulting in the missed detection of 176 Sanger-confirmed variants, the majority in complex genomic regions (n = 114) and mosaic mutations (n = 7). The data illustrate the importance of setting quality thresholds for panel testing only after thousands of samples have been processed and the necessity of Sanger confirmation of NGS variants to maintain the highest possible sensitivity

On the scattering of elastic waves from a non-axisymmetric defect in a coated pipe

Viscoelastic coatings are often used to protect pipelines in the oil and gas industry. However, over time defects and areas of corrosion often form in these pipelines and so it is desirable to monitor the structural integrity of these coated pipes using techniques similar to those used on uncoated pipelines. A common approach is to use ultrasonic guided waves that work on the pulse-echo principle; however, the energy in the guided waves can be heavily attenuated by the coating and so significantly reduce the effective range of these techniques. Accordingly, it is desirable to develop a better understanding of how these waves propagate in coated pipes with a view to optimising test methodologies, and so this article uses a hybrid SAFE-finite element approach to model scattering from non-axisymmetric defects in coated pipes. Predictions are generated in the time and frequency domain and it is shown that the longitudinal family of modes is likely to have a longer range in coated pipes when compared to torsional modes. Moreover, it is observed that the energy velocity of modes in a coated pipe is very similar to the group velocity of equivalent modes in uncoated pipes. It is also observed that the coating does not induce any additional mode conversion over and above that seen for an uncoated pipe when an incident wave is scattered by a defect. Accordingly, it is shown that when studying coated pipes one need account only for the attenuation imparted by the coating so that one may normally neglect the effect of coating on modal dispersion and scattering

Methylthioadenosine reprograms macrophage activation through adenosine receptor stimulation

Regulation of inflammation is necessary to balance sufficient pathogen clearance with excessive tissue damage. Central to regulating inflammation is the switch from a pro-inflammatory pathway to an anti-inflammatory pathway. Macrophages are well-positioned to initiate this switch, and as such are the target of multiple therapeutics. One such potential therapeutic is methylthioadenosine (MTA), which inhibits TNFα production following LPS stimulation. We found that MTA could block TNFα production by multiple TLR ligands. Further, it prevented surface expression of CD69 and CD86 and reduced NF-KB signaling. We then determined that the mechanism of this action by MTA is signaling through adenosine A2 receptors. A2 receptors and TLR receptors synergized to promote an anti-inflammatory phenotype, as MTA enhanced LPS tolerance. In contrast, IL-1β production and processing was not affected by MTA exposure. Taken together, these data demonstrate that MTA reprograms TLR activation pathways via adenosine receptors to promote resolution of inflammation. © 2014 Keyel et al

Ancestry-informative markers for African Americans based on the Affymetrix Pan-African genotyping array

Genetic admixture has been utilized as a tool for identifying loci associated with complex traits and diseases in recently admixed populations such as African Americans. In particular, admixture mapping is an efficient approach to identifying genetic basis for those complex diseases with substantial racial or ethnic disparities. Though current advances in admixture mapping algorithms may utilize the entire panel of SNPs, providing ancestry-informative markers (AIMs) that can differentiate parental populations and estimate ancestry proportions in an admixed population may particularly benefit admixture mapping in studies of limited samples, help identify unsuitable individuals (e.g., through genotyping the most informative ancestry markers) before starting large genome-wide association studies (GWAS), or guide larger scale targeted deep re-sequencing for determining specific disease-causing variants. Defining panels of AIMs based on commercial, high-throughput genotyping platforms will facilitate the utilization of these platforms for simultaneous admixture mapping of complex traits and diseases, in addition to conventional GWAS. Here, we describe AIMs detected based on the Shannon Information Content (SIC) or Fst for African Americans with genome-wide coverage that were selected from ∼2.3 million single nucleotide polymorphisms (SNPs) covered by the Affymetrix Axiom Pan-African array, a newly developed genotyping platform optimized for individuals of African ancestry

Dynamic Response and Its Frequency Domain Characteristics of Lateritic Soil Subgrade under Traffic Load during Construction

Field tests were carried out on the compacted lateritic soil subgrade of Laibin-Mashan expressway in Guangxi Province to obtain the vertical vibration acceleration and dynamic stress amplitude of each test point under different axle loads and different driving speeds. The distribution law of the dynamic response and its frequency domain characteristics obtained by wavelet analysis emerged. The vibration of the subgrade is clearly aggravated by the increase of speed and load. Specifically, the acceleration of vehicle speed from 20 km/h to 40 km/h has a prominent effect on the vibration of subgrade, and the influence of speed on the vibration of subgrade decreases with subgrade depth. The acceleration has the greatest impact on the vibration energy in the third and fourth frequency bands

Ancestry-informative markers for African Americans based on the Affymetrix Pan-African genotyping array PrePrints Ancestry-Informative Markers for African Americans Based on the Affymetrix Pan-African Genotyping Array

Genetic admixture has been utilized as a tool for identifying loci associated with complex traits and diseases in recently admixed populations such as African Americans. In particular, admixture mapping is an efficient approach to identifying genetic basis for those complex diseases with substantial racial or ethnic disparities