The role of exome sequencing in newborn screening for inborn errors of metabolism

Public health newborn screening (NBS) programs provide population-scale ascertainment of rare, treatable conditions that require urgent intervention. Tandem mass spectrometry (MS/MS) is currently used to screen newborns for a panel of rare inborn errors of metabolism (IEMs)1-4. The NBSeq project evaluated whole-exome sequencing (WES) as an innovative methodology for NBS. We obtained archived residual dried blood spots and data for nearly all IEM cases from the 4.5 million infants born in California between mid-2005 and 2013 and from some infants who screened positive by MS/MS, but were unaffected upon follow-up testing. WES had an overall sensitivity of 88% and specificity of 98.4%, compared to 99.0% and 99.8%, respectively for MS/MS, although effectiveness varied among individual IEMs. Thus, WES alone was insufficiently sensitive or specific to be a primary screen for most NBS IEMs. However, as a secondary test for infants with abnormal MS/MS screens, WES could reduce false-positive results, facilitate timely case resolution and in some instances even suggest more appropriate or specific diagnosis than that initially obtained. This study represents the largest, to date, sequencing effort of an entire population of IEM-affected cases, allowing unbiased assessment of current capabilities of WES as a tool for population screening

Kinetics of thermally activated processes in cordierite-based ceramics

Thermally activated processes in cordierite-based ceramics were investigated to determine the effect of the mechanical activation and the addition of TeO2 on kinetic and thermodynamic parameters of these processes. Using a combination of dilatometry and DTA measurements in the 100–1400 °C temperature range, it was established that both the mechanical activation and the addition of TeO2 have a significant effect on processes in cordierite-based ceramics. A combination of 5 mass% addition of TeO2 and mechanical activation for 40 min reduced the sintering temperature of cordierite ceramics to around 1100 °C. In addition, the analysis of DTA measurements of mechanically activated samples indicates that the mechanical activation leads to intensification of the cordierite formation through an increase in concentration of surface defects and an increase in grain contact surface in the initial powder.Peer-reviewed manuscript: [http://aspace.agrif.bg.ac.rs/handle/123456789/5733