Current Practices in LC-MS Untargeted Metabolomics: A Scoping Review on the Use of Pooled Quality Control Samples.

Untargeted metabolomics is an analytical approach with numerous applications serving as an effective metabolic phenotyping platform to characterize small molecules within a biological system. Data quality can be challenging to evaluate and demonstrate in metabolomics experiments. This has driven the use of pooled quality control (QC) samples for monitoring and, if necessary, correcting for analytical variance introduced during sample preparation and data acquisition stages. Described herein is a scoping literature review detailing the use of pooled QC samples in published untargeted liquid chromatography-mass spectrometry (LC-MS) based metabolomics studies. A literature query was performed, the list of papers was filtered, and suitable articles were randomly sampled. In total, 109 papers were each reviewed by at least five reviewers, answering predefined questions surrounding the use of pooled quality control samples. The results of the review indicate that use of pooled QC samples has been relatively widely adopted by the metabolomics community and that it is used at a similar frequency across biological taxa and sample types in both small- and large-scale studies. However, while many studies generated and analyzed pooled QC samples, relatively few reported the use of pooled QC samples to improve data quality. This demonstrates a clear opportunity for the field to more frequently utilize pooled QC samples for quality reporting, feature filtering, analytical drift correction, and metabolite annotation. Additionally, our survey approach enabled us to assess the ambiguity in the reporting of the methods used to describe the generation and use of pooled QC samples. This analysis indicates that many details of the QC framework are missing or unclear, limiting the reader's ability to determine which QC steps have been taken. Collectively, these results capture the current state of pooled QC sample usage and highlight existing strengths and deficiencies as they are applied in untargeted LC-MS metabolomics.

Progress towards an OECD reporting framework for transcriptomics and metabolomics in regulatory toxicology.

Omics methodologies are widely used in toxicological research to understand modes and mechanisms of toxicity. Increasingly, these methodologies are being applied to questions of regulatory interest such as molecular point-of-departure derivation and chemical grouping/read-across. Despite its value, widespread regulatory acceptance of omics data has not yet occurred. Barriers to the routine application of omics data in regulatory decision making have been: 1) lack of transparency for data processing methods used to convert raw data into an interpretable list of observations; and 2) lack of standardization in reporting to ensure that omics data, associated metadata and the methodologies used to generate results are available for review by stakeholders, including regulators. Thus, in 2017, the Organisation for Economic Co-operation and Development (OECD) Extended Advisory Group on Molecular Screening and Toxicogenomics (EAGMST) launched a project to develop guidance for the reporting of omics data aimed at fostering further regulatory use. Here, we report on the ongoing development of the first formal reporting framework describing the processing and analysis of both transcriptomic and metabolomic data for regulatory toxicology. We introduce the modular structure, content, harmonization and strategy for trialling this reporting framework prior to its publication by the OECD.

Boranophosphate siRNA-aptamer chimeras for tumor-specific downregulation of cancer receptors and modulators.

There is a need for novel, effective, and cell- and gene-specific therapeutics for cancer. Modified oligonucleotides can be used to modulate specifically and potently the expression of several genes that are upregulated in breast and prostate cancer and have been found to be causal to the tumor phenotype. Synergistic downregulation of these genes may be a potent therapeutic intervention. We are investigating the use of boranophosphate (BP) analogues of RNA as promising candidates for enhancing the potential of three relatively new, gene-specific, anticancer strategies: (1) Tumor-targeted borane siRNA against a combination of genes that control metabolism and transduction; (2) Tumor-specific modified aptamers against prostate specific membrane antigen (PSMA) and ERB2 in breast cancer as delivery agents; and (3) Cancer cell obliteration by cell-specific radiation therapy: Boron-Neutron-Capture-Therapy.

Silver sulfide nanoparticle assembly obtained by reacting an assembled silver nanoparticle template with hydrogen sulfide gas.

A fast, simple procedure is described for obtaining an assembly of silver sulfide nanoparticles (Ag(2)S NPs) on a glass substrate through reaction of a template of an assembled layer of silver nanoparticles (Ag NPs) with hydrogen sulfide (H(2)S) gas. The Ag NP template was prepared by assembling a monolayer of spherical Ag NPs (mean diameter of 7.4 nm) on a polyethylenimine-treated glass substrate. Exposure to pure H(2)S for 10 min converted the Ag NPs of the template to Ag(2)S NPs. The resulting Ag(2)S NP assembly, which retains the template nanostructure and particle distribution, was characterized by optical absorption spectroscopy, atomic force microscopy, transmission electron microscopy (TEM), scanning high resolution TEM, energy dispersive x-ray spectroscopy and x-ray photoelectron spectroscopy. The Ag(2)S NPs have a crystal structure of monoclinic acanthite, and while they retained the spherical shape of the original Ag NPs, their mean particle size increased to 8.4 nm due to changes to the crystal structure when the Ag NPs are converted into Ag(2)S NPs. The measured optical absorption edge of the Ag(2)S NP assembly indicated an indirect interband transition with a band gap energy of 1.71 eV. The Ag(2)S NP assembly absorbed light with wavelengths below 725 nm, and the absorbance increased monotonically toward the UV region.