Semi-Quantitative MALDI Measurements of Blood-Based Samples for Molecular Diagnostics

Accurate and precise measurement of the relative protein content of blood-based samples using mass spectrometry is challenging due to the large number of circulating proteins and the dynamic range of their abundances. Traditional spectral processing methods often struggle with accurately detecting overlapping peaks that are observed in these samples. In this work, we develop a novel spectral processing algorithm that effectively detects over 1650 peaks with over 3.5 orders of magnitude in intensity in the 3 to 30 kD m/z range. The algorithm utilizes a convolution of the peak shape to enhance peak detection, and accurate peak fitting to provide highly reproducible relative abundance estimates for both isolated peaks and overlapping peaks. We demonstrate a substantial increase in the reproducibility of the measurements of relative protein abundance when comparing this processing method to a traditional processing method for sample sets run on multiple matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) instruments. By utilizing protein set enrichment analysis, we find a sizable increase in the number of features associated with biological processes compared to previously reported results. The new processing method could be very beneficial when developing high-performance molecular diagnostic tests in disease indications

A Genetic Variant in the BCL2 Gene Associates with Adalimumab Response in Hidradenitis Suppurativa Clinical Trials and Regulates Expression of BCL2

Hidradenitis suppurativa is a chronic skin disease with a significant genetic component and prevalence from 0.5% to 4%. Adalimumab is the only treatment approved by either the European Medicines Agency or the U.S. Food and Drug Administration for the management of moderate to severe hidradenitis suppurativa. To identify genetic variants associated with adalimumab response, we performed a genome-wide association study (GWAS) from the most extensive two phase 3 hidradenitis suppurativa clinical trials (PIONEER I and II) to date. Through direct genotyping and imputation, we tested almost 7 million genetic variants with minor allele frequency > 5% and identified one single linkage disequilibrium block, located in the intron of the BCL2 gene, which reached genome-wide significance (lead single-nucleotide polymorphism, rs59532114; P = 2.35E–08). Bioinformatic analysis and functional genomics experiments suggested a correlation of the most strongly associated single-nucleotide polymorphism minor allele with increased BCL2 gene and protein expressions in hair follicle tissues. In reciprocal knockdown experiments, we found that BCL2 is down-regulated by TNF inhibition. These results highlight a pathway that involves BCL2 in response to adalimumab. Further work is required to determine how this pathway influences adalimumab effectiveness in patients with hidradenitis suppurativa

Constructive approaches towards water treatment works sludge management : an international review of beneficial re-uses

Till date, virtually all known drinking water processing systems generate an enormous amount of residual sludge, and what else to do with this rapidly increasing 'waste' stream in an economic and environmentally sustainable manner remains a significant environmental issue. Perhaps, the realization of this fact has led to series of concerted efforts aimed at beneficial re-uses in an effort to close the loop between efficient water treatment and sustainable sludge management. This paper therefore presents a comprehensive review of available literature on attempts at beneficial reuses of water treatment plant sludge, in an effort to provide a compendium of recent and past developments, and update our current state of knowledge. Four broad categories of uses, which included over eleven possible ways in which waterworks sludges can be reused were identified and examined. Obvious advantages of such reuse options were highlighted and knowledge gaps identified. Future issues that will assist in the development of sustainable waterworks sludge management options with a multi-prong approach were equally discussed.Other funderEnvironmental Protection Agencyke,ti,ab,SB-09/09/201