Advances in mass spectrometry-based cancer research and analysis: from cancer proteomics to clinical diagnostics

Introduction: The last 20 years have seen significant improvements in the analytical capabilities of biological mass spectrometry. Studies using advanced mass spectrometry (MS) have resulted in new insights into cell biology and the aetiology of diseases as well as its use in clinical applications. Areas Covered: This review will discuss recent developments in MS-based technologies and their cancer-related applications with a focus on proteomics. It will also discuss the issues around translating the research findings to the clinic and provide an outline of where the field is moving. Expert Opinion: Proteomics has been problematic to adapt for the clinical setting. However, MS-based techniques continue to demonstrate potential in novel clinical uses beyond classical cancer proteomics

Computational and Systems Biology Advances to Enable Bioagent-Agnostic Signatures

Enumerated threat agent lists have long driven biodefense priorities. The global SARS-CoV-2 pandemic demonstrated the limitations of searching for known threat agents as compared to a more agnostic approach. Recent technological advances are enabling agent-agnostic biodefense, especially through the integration of multi-modal observations of host-pathogen interactions directed by a human immunological model. Although well-developed technical assays exist for many aspects of human-pathogen interaction, the analytic methods and pipelines to combine and holistically interpret the results of such assays are immature and require further investments to exploit new technologies. In this manuscript, we discuss potential immunologically based bioagent-agnostic approaches and the computational tool gaps the community should prioritize filling

Applications of liquid chromatography coupled to mass spectrometry-based metabolomics in clinical chemistry and toxicology: A review.

International audienceThe metabolome is the set of small molecular mass organic compounds found in a given biological media. It includes all organic substances naturally occurring from the metabolism of the studied living organism, except biological polymers, but also xenobiotics and their biotransformation products. The metabolic fingerprints of biofluids obtained by mass spectrometry (MS) or nuclear magnetic resonance (NMR)-based methods contain a few hundreds to thousands of signals related to both genetic and environmental contributions. Metabolomics, which refers to the untargeted quantitative or semi-quantitative analysis of the metabolome, is a promising tool for biomarker discovery. Although proof-of-concept studies by metabolomics-based approaches in the field of toxicology and clinical chemistry have initially been performed using NMR, the use of liquid chromatography hyphenated to mass spectrometry (LC/MS) has increased over the recent years, providing complementary results to those obtained with other approaches. This paper reviews and comments the input of LC/MS in this field. We describe here the overall process of analysis, review some seminal papers in the field and discuss the perspectives of metabolomics for the biomonitoring of exposure and diagnosis of diseases

Mid-Scale Instrumentation: Regional Facilities to Address Grand Challenges in Chemistry

A regional workshop sponsored by the National Science Foundation, Arlington, Virginia, September 29-30, 2016. To determine what needs and opportunities might exist for mid-scale instrumentation (MSI), two workshops were held in fall of 2016 to explore opportunities within the discipline that could be provided by such investment. One workshop was convened to explore the need for co-localization of existing instrumentation at a regional or cyber-enabled facilities (addressed in this report, “Mid-Scale Instrumentation: Regional Facilities to Address Grand Challenges in Chemistry”). In this report, we identify different areas where investment in such MSI facilities would be highly beneficial. These appear as six “grand challenges” that can be summarized here as follows: 1. Structure and dynamics at interfaces 2. Highly parallel chemical synthesis and characterization 3. Transient intermediates 4. New science arising from the characterization of heterogeneous mixtures 5. Multi-scale dynamics of complex systems: integrating transport with reaction 6. Structure-function relationship in disordered and/or heterogeneous system

Advances in chemical and biological methods to identify microorganisms—from past to present

Fast detection and identification of microorganisms is a challenging and significant feature from industry to medicine. Standard approaches are known to be very time-consuming and labor-intensive (e.g., culture media and biochemical tests). Conversely, screening techniques demand a quick and low-cost grouping of bacterial/fungal isolates and current analysis call for broad reports of microorganisms, involving the application of molecular techniques (e.g., 16S ribosomal RNA gene sequencing based on polymerase chain reaction). The goal of this review is to present the past and the present methods of detection and identification of microorganisms, and to discuss their advantages and their limitations.C.F.R. would like to thank the Portuguese Foundation for Science and Technology (FCT–Portugal) for the C.F.R. for the project UID/EQU/00511/2019—Laboratory for Process Engineering, Environment, Biotechnology, and Energy—LEPABE funded by national funds through FCT/MCTES (PIDDAC) and N.M. for the Strategic project ref. UID/BIM/04293/2013 and “NORTE2020 - Programa Operacional Regional do Norte” (NORTE-01-0145-FEDER-000012)

An update on MALDI Mass Spectrometry based technology for the analysis of fingermarks - stepping into operational deployment

Since in 2009, when Matrix Assisted Laser Desorption Ionisation Mass Spectrometry Imaging (MALDI MSI) was firstly reported for the molecular mapping of latent fingermarks, the range of information and operational capabilities have steadily increased. Pioneering work from our Fingermark Research Group exploited different modalities, including Profiling (MALDI MSP), tandem mass spectrometry (MS/MS) and Ion Mobility MS/MS; a number of methodologies were also developed to conquer a main challenge, namely profiling the suspect and their actions prior to or whilst committing the crime. Suspect profiling here is no longer based on behavioural science but complements this discipline and the investigations by detecting and visualising the molecular make-up of fingermarks onto the identifying ridges. This forensic opportunity provides the link between the biometric information (ridge detail) and the corpus delicti or intelligence on the circumstances of the crime. In 2013, a review was published covering the research work and developments of four years supported by the Home Office, UK and the local regional Police with some insights (and comparison) into similar research being reported employing other mass spectrometric techniques. The present review is an extensive update on the MALDI MS based methods' achievements, limitations and work in progress; it also offers an outlook on further necessary research into this subject. The main highlights are the increased number of possible information retrievable around a suspect and the more extended compatibility of this technology. The latter has allowed MALDI MS based methods to integrate well with current forensic fingerprinting, leading to the investigation of real police casework

Exploring bonding interactions of biochemical relevance in silicon, platinum(II) and iron(III) positively charged species

Elements playing a biological role that are present in nature or in synthetic drugs, such as silicon, platinum(II) and iron(III) usually appear coordinated to ligands in more or less composite molecular architectures. This notion is particularly true when a metal ion is placed in the active center of an enzyme or otherwise integrated into simple biomolecules and proteins. Whereas multifaceted factors affect a charged (metal) centre in a biological environment, the gas-phase provides an interesting medium for elucidating intrinsic interactions between metal ions and biological targets. The idea underlying this doctoral thesis is to highlight how state of the art techniques combining mass spectrometry, IR spectroscopy and computational chemistry can be applied to the study of ionic complexes in an isolated state. In a first section the reactivity behavior of gaseous complexes from the (CH3)3Si+ addition to acetylene has been fully explored by FT-ICR mass spectrometry and ab initio calculations. In this way the C5H11Si+ potential energy surface has been elucidated and the computational results nicely account for the experimental evidence showing an isomerization process from a primarily formed complex (a β-silyl-substituted vinyl cation acquiring an asymmetric cyclic geometry) to CH2=C(CH3)-Si(CH3)2+ silyl cation. The computational methods tested in dealing with the C5H11Si+ ion problem have been further applied to more challenging systems. In a second and third section a comprehensive investigation of the structural features of the key intermediates which are formed from cisplatin by replacement of chloro ligands by water or methionine is described. Here the experimental approach has involved vibrational spectroscopy carried out with a recently designed and assembled apparatus. The NH/OH stretching region has been found highly structurally diagnostic in the aqua complexes where hydrogen bonding interactions are crucial in determining relative conformer stability. The infrared characterization of the monofunctional adducts of platinum(II) drugs with methionine has led to identify distinct modes of interaction with cisplatin and transplatin derived species. In fact, the preferred ligand atom (S or N) seems to be depending on the specific isomer (cis- or trans-) that is reacting with the metal. Cisplatin and transplatin derived species have been sampled both experimentally and computationally, taking into account relativistic effects in the heavy metal. In a fourth task the binding properties of azole ligands toward ferric heme have been examined. Starting from simple ligands such as pyridine, 1-methylimidazole and 1H-1,2,4-triazole, the focus was then directed to imidazole- and triazole-based antifungal drugs. These drugs are known to act as inhibitors of CYP51enzyme, through binding to the heme prosthetic group. Relative binding energies were determined experimentally by energy variable collision induced dissociation experiments performed on the selected ionic complexes and evaluated theoretically by Car-Parrinello molecular dynamics calculations. To this end, theoretical investigations were carried out during a training period spent at the “Parc Cientific de Barcelona”, under the supervision of Research Professor Carme Rovira. Imidazole-based drugs consistently display higher dissociation energies when compared to triazole-based drugs

Detection of Microorganisms using MALDI and ion mobility mass spectrometry

Matrix-assisted laser ablation desorption ionization MALDI and ion mobility (IM) MALDI mass spectrometry (MS) were used for the detection and identification of microorganisms. MALDI MS is an analytical tool that separates ions by their mass-to-charge ratio (m/z) and is routinely used for bioanalysis because of its sensitivity, selectivity, general applicability, and tolerance to impurities. Ion mobility is a gas phase technique that separates ions based on their charge and collision cross-section. In this research, MALDI-TOF MS and MALDI-IM-TOF MS analysis were conducted in parallel to assess the effectiveness of MALDI-IM-TOF MS for microorganism identification. Whole cell bacteria Escherichia coli strain W 9637 and Bacillus subtilis 6633 were prepared and analyzed using both MALDI-TOF MS and MALDI-IM-TOF MS. The signals from both analysis methods were identified using a microbial database. Vacuum ultraviolet (VUV) post-ionization MALDI-IM-TOF MS was also used and additional peaks that could not be detected using MALDI-TOF MS and MALDI-IM-TOF MS were observed from B. subtilis. MALDI MS was used in combination with mass spectral fingerprinting software for the identification of whole cell bacteria in the presence of potential environmental interferants. Whole bacteria were analyzed in the presence of fumed silica, bentonite, and pollen from Juglans nigra (black walnut) at various mass ratios. The effect of the interferants on the identifications of bacteria at the genus and species level was evaluated using the bacteria fingerprinting software MB. The results showed that correct species identification for E. coli 35218, could be determined with fumed silica, bentonite, and pollen at a mass ratio of 1:1; whereas, at the same mass ratio, with diesel particulate, only genus identification could be made. Species identification for E. aerogenes 13048 with fumed silica and pollen at a mass ratio of 1:1 was achieved. Genus identification was determined for E.aerogenes with bentonite and diesel particulate. As the mass ratio of the interferant increased, the likelihood of species identification decreased with the exception of E. aerogenes with fumed silica and pollen. Under ambient conditions, laser ablation sample transfer using a mid-infrared laser at 2.94 ƒÝm was used to ablate gram-negative E. coli 35218 and gram-positive B. cereus 11178 bacterial colony particulate from a petri dish into a solvent droplet suspended above the petri dish. The solvent droplet containing the captured material was then transferred to a nanostructured-assisted laser desorption ionization (NALDI) target for analysis on a matrix-assisted laser desorption ionization (MALDI) time-of-flight (TOF) mass spectrometer (MS). Several peaks that were observed in the NALDI spectra of both gram-negative and gram-positive correspond to phospholipid classes, phosphatidylethanolamine (PE) and phosphatidylglycerol (PG). Additional phospholipids diglycosyldiglyceride (DGDG), triacylglyceride (TAG) and a lipopeptide, which are typically found in gram-positive bacteria were observed in the NALDI spectrum of B. cereus. Using LAST NALDI, phospholipids could be identified from both bacterial species without any sample pretreatment