Multi-Institutional FASTQ File Exchange as a Means of Proficiency Testing for Next-Generation Sequencing Bioinformatics and Variant Interpretation

Next-generation sequencing is becoming increasingly common in clinical laboratories worldwide and is revolutionizing clinical molecular testing. However, the large amounts of raw data produced by next-generation sequencing assays and the need for complex bioinformatics analyses present unique challenges. Proficiency testing in clinical laboratories has traditionally been designed to evaluate assays in their entirety; however, it can be alternatively applied to separate assay components. We developed and implemented a multi-institutional proficiency testing approach to directly assess custom bioinformatics and variant interpretation processes. Six clinical laboratories, all of which use the same commercial library preparation kit for next-generation sequencing analysis of tumor specimens, each submitted raw data (FASTQ files) from four samples. These 24 file sets were then deidentified and redistributed to five of the institutions for analysis and interpretation according to their clinically validated approach. Among the laboratories, there was a high rate of concordance in the calling of single-nucleotide variants, in particular those we considered clinically significant (100% concordance). However, there was significant discordance in the calling of clinically significant insertions/deletions, with only two of seven being called by all participating laboratories. Missed calls were addressed by each laboratory to improve their bioinformatics processes. Thus, through our alternative proficiency testing approach, we identified the bioinformatic detection of insertions/deletions as an area of particular concern for clinical laboratories performing next-generation sequencing testing

ATM variants 7271T>G and IVS10-6T>G among women with unilateral and bilateral breast cancer

Recent reports suggest that two ATM gene mutations, 7271T>G and IVS10-6T>G, are associated with a high risk of breast cancer among multiple-case families. To assess the importance of these two mutations in another 'high-risk' group, young women (under age 51) with multiple primaries, we screened a large population-based series of young women with bilateral breast cancer and compared the frequency of these mutations among similar women diagnosed with unilateral breast cancer. The 1149 women included were enrolled in an ongoing population-based case-control study of the genetic factors that contribute to bilateral breast cancer; they were not selected on the basis of family history of cancer. Screening for 7271T>G and IVS10-6T>G ATM gene mutations was conducted using DHPLC followed by direct sequencing. The 7271T>G mutation was detected in one out of 638 (0.2%) women with unilateral breast cancer and in none of the bilateral cases, and the IVS10-6T>G mutation in one out of 511 (0.2%) bilateral and in eight out of 638 (1.3%) unilateral breast cancer cases. Carriers of either mutation were not limited to women with a family history. Given the likelihood that young women with bilateral breast cancer have a genetic predisposition, the observed mutation distribution is contrary to that expected if these two mutations were to play an important role in breast carcinogenesis among individuals at high risk

Computational Refinement of Functional Single Nucleotide Polymorphisms Associated with ATM Gene

gene are the most common forms of genetic variations that account for various forms of cancer. However, the extent to which SNPs interferes with the gene regulation and affects cancer susceptibility remains largely unknown. gene. gene function can aid in better understanding of genetic differences in disease susceptibility

Measuring indirect economic impacts arising from transportation investment by a SCGE model

The objective of this paper is threefold. First, the paper presents a regionally disaggregated CGE model, in which “a region” is defined as a sub-area or a zone within a country or a particular area and the spatial dimension of the economy is explicitly included. In such a spatial CGE model, the estimation of interzonal trade flows has a critically important role: with the presence of shipping cost, suppliers would impose the cost on their sales prices for covering that cost, which changes the product shipping pattern for each type of commodity or service and thereby affects the efficiency of regional economies. Second, the paper proposes a new approach that links travel delay (attributable to congestion) and business productivity. Transportation investment changes the relative economic advantage that each region has through the changes in accessibility to material/service markets and labor markets. To estimate the rate return on transportation investment to reduce congestion, it is necessary to estimate how the specialized transportation policy to reduce congestion has economic impacts on regional economies. Finally, the paper explores the values of economic impacts measured by an application of the model to Tokai ring road project, which is an on-going project to build an expressway of about 160km in length connecting annularly many cities in Tokai region

Sul Numero Cromosomico di Matteuccia Struthiopteris

RIASSUNTOIn due esemplari di Matteuccia struthiopteris (L.) Todaro coltivati nell'Orto Botanico dell'Universita di Firenze lo studio della meiosi di molte cellule madri delle spore ha messo in luce la presenza di 39 bivalentti. Gli Autori che precedentemente hanno studiato la specie riportano n=40 oppure n=c.40