Open Access Repository-Scale Propagated Nearest Neighbor Suspect Spectral Library for Untargeted Metabolomics

Abstract Despite the increasing availability of tandem mass spectrometry (MS/MS) community spectral libraries for untargeted metabolomics over the past decade, the majority of acquired MS/MS spectra remain uninterpreted. To further aid in interpreting unannotated spectra, we created a nearest neighbor suspect spectral library, consisting of 87,916 annotated MS/MS spectra derived from hundreds of millions of public MS/MS spectra. Annotations were propagated based on structural relationships to reference molecules using MS/MS-based spectrum alignment. We demonstrate the broad relevance of the nearest neighbor suspect spectral library through representative examples of propagation-based annotation of acylcarnitines, bacterial and plant natural products, and drug metabolism. Our results also highlight how the library can help to better understand an Alzheimer’s brain phenotype. The nearest neighbor suspect spectral library is openly available through the GNPS platform to help investigators hypothesize candidate structures for unknown MS/MS spectra in untargeted metabolomics data

Quality control in mass spectrometry-based proteomics

Mass spectrometry is a highly complex analytical technique and mass spectrometry-based proteomics experiments can be subject to a large variability, which forms an obstacle to obtaining accurate and reproducible results. Therefore, a comprehensive and systematic approach to quality control is an essential requirement to inspire confidence in the generated results. A typical mass spectrometry experiment consists of multiple different phases including the sample preparation, liquid chromatography, mass spectrometry, and bioinformatics stages. We review potential sources of variability that can impact the results of a mass spectrometry experiment occurring in all of these steps, and we discuss how to monitor and remedy the negative influences on the experimental results. Furthermore, we describe how specialized quality control samples of varying sample complexity can be incorporated into the experimental workflow and how they can be used to rigorously assess detailed aspects of the instrument performance

Endoplasmic Reticulum-Mitochondria Communication Through Ca2+ signaling: the importance of mitochondria associated membranes (MAMs)

The execution of proper Ca2+ signaling requires close apposition between the endoplasmic reticulum (ER) and mitochondria. Hence, Ca2+ released from the ER is "quasi-synaptically" transferred to mitochondrial matrix, where Ca2+ stimulates mitochondrial ATP synthesis by activating the tricarboxylic acid (TCA) cycle. However, when the Ca2+ transfer is excessive and sustained, mitochondrial Ca2+ overload induces apoptosis by opening the mitochondrial permeability transition pore. A large number of regulatory proteins reside at mitochondria-associated ER membranes (MAMs) to maintain the optimal distance between the organelles and to coordinate the functionality of both ER and mitochondrial Ca2+ transporters or channels. In this chapter, we discuss the different pathways involved in the regulation of ER-mitochondria Ca2+ flux and describe the activities of the various Ca2+ players based on their primary intra-organelle localization.status: publishe

Towards a History of Mass Violence in the Etat Indépendant du Congo, 1885-1908

The present article provides an up-to-date scholarly introduction to mass violence in the Etat Indépendant du Congo (Congo Free State, EIC). Its aims are twofold: to offer a point of access to the extensive literature and historical debates on the subject, and to make the case for exchanging the currently prevalent top-down narrative, with its excessive focus on King Leopold's character and motives, for one which considers the EIC's culture of violence as a multicausal, broadly based and deeply engrained social phenomenon. The argument is divided into five sections. Following a general outline of the EIC's violent system of administration, I discuss its social and demographic impact (and the controversy which surrounds it) to bring out the need for more regionally focused and context sensitive studies. The dispute surrounding demographics demonstrates that what is fundamentally at stake is the place the EIC's extreme violence should occupy in the history of European ‘modernity’. Since approaches which hinge on Leopoldian exceptionalism are particularly unhelpful in clarifying this issue, I pause to reflect on how such approaches came to dominate the distinct historiographical traditions which emerged in Belgium and abroad before moving on to a more detailed exploration of a selection of causes underlying the EIC's violent nature. While state actors remain in the limelight, I shift the focus from the state as a singular, normative agent, towards the existence of an extremely violent society in which various individuals and social groups within and outside of the state apparatus committed violent acts for multiple reasons. As this argument is pitched at a high level of abstraction, I conclude with a discussion of available source material with which it can be further refined and updated

Proteomics Standards Initiative: Fifteen Years of Progress and Future Work

The Proteomics Standards Initiative (PSI) of the Human Proteome Organization (HUPO) has now been developing and promoting open community standards and software tools in the field of proteomics for 15 years. Under the guidance of the chair, cochairs, and other leadership positions, the PSI working groups are tasked with the development and maintenance of community standards via special workshops and ongoing work. Among the existing ratified standards, the PSI working groups continue to update PSI-MI XML, MITAB, mzML, mzIdentML, mzQuantML, mzTab, and the MIAPE (Minimum Information About a Proteomics Experiment) guidelines with the advance of new technologies and techniques. Furthermore, new standards are currently either in the final stages of completion (proBed and proBAM for proteogenomics results as well as PEFF) or in early stages of design (a spectral library standard format, a universal spectrum identifier, the qcML quality control format, and the Protein Expression Interface (PROXI) web services Application Programming Interface). In this work we review the current status of all of these aspects of the PSI, describe synergies with other efforts such as the ProteomeXchange Consortium, the Human Proteome Project, and the metabolomics community, and provide a look at future directions of the PSI

Proteomics standards initiative’s ProForma 2.0 : unifying the encoding of proteoforms and peptidoforms

It is important for the proteomics community to have a standardized manner to represent all possible variations of a protein or peptide primary sequence, including natural, chemically induced, and artifactual modifications. The Human Proteome Organization Proteomics Standards Initiative in collaboration with several members of the Consortium for Top-Down Proteomics (CTDP) has developed a standard notation called ProForma 2.0, which is a substantial extension of the original ProForma notation developed by the CTDP. ProForma 2.0 aims to unify the representation of proteoforms and peptidoforms. ProForma 2.0 supports use cases needed for bottom-up and middle-/top-down proteomics approaches and allows the encoding of highly modified proteins and peptides using a human- and machine-readable string. ProForma 2.0 can be used to represent protein modifications in a specified or ambiguous location, designated by mass shifts, chemical formulas, or controlled vocabulary terms, including cross-links (natural and chemical) and atomic isotopes. Notational conventions are based on public controlled vocabularies and ontologies. The most up-to-date full specification document and information about software implementations are available at http://psidev.info/proforma

Proteomics Standards Initiative\u27s ProForma 2.0: Unifying the Encoding of Proteoforms and Peptidoforms.

It is important for the proteomics community to have a standardized manner to represent all possible variations of a protein or peptide primary sequence, including natural, chemically induced, and artifactual modifications. The Human Proteome Organization Proteomics Standards Initiative in collaboration with several members of the Consortium for Top-Down Proteomics (CTDP) has developed a standard notation called ProForma 2.0, which is a substantial extension of the original ProForma notation developed by the CTDP. ProForma 2.0 aims to unify the representation of proteoforms and peptidoforms. ProForma 2.0 supports use cases needed for bottom-up and middle-/top-down proteomics approaches and allows the encoding of highly modified proteins and peptides using a human- and machine-readable string. ProForma 2.0 can be used to represent protein modifications in a specified or ambiguous location, designated by mass shifts, chemical formulas, or controlled vocabulary terms, including cross-links (natural and chemical) and atomic isotopes. Notational conventions are based on public controlled vocabularies and ontologies. The most up-to-date full specification document and information about software implementations are available at http://psidev.info/proforma