Cross-platform proteomics to advance genetic prioritisation strategies

Discovery of protein quantitative trait loci (pQTLs) has been enabled by affinity-based proteomic techniques and is increasingly used to guide genetically informed drug target evaluation. Large-scale proteomic data are now being created, but systematic, bidirectional assessment of platform differences is lacking, restricting clinical translation. We compared genetic, technical, and phenotypic determinants of 871 protein targets measured using both aptamer- (SomaScan® Platform v4) and antibody-based (Olink) assays in up to 10,708 individuals. Correlations coefficients for overlapping protein targets varied widely (median 0.38, IQR: 0.08-0.64). We found that 64% of pQTLs were shared across both platforms among all identified 608 cis- and 1,315 trans-pQTLs with sufficient power for replication, but with correlations of effect estimates being lower than previously reported (cis: 0.41, trans: 0.34). We identified technical, protein, and variant characteristics that contributed significantly to platform differences and found contradicting phenotypic associations attributable to those. We demonstrate how integrating phenomic and gene expression data improves genetic prioritisation strategies, including platform-specific pQTLs.

Review: Proteomic Techniques for the Development of Flood-Tolerant Soybean

Soybean, which is rich in protein and oil as well as phytochemicals, is cultivated in several climatic zones. However, its growth is markedly decreased by flooding stress, which is caused by climate change. Proteomic techniques were used for understanding the flood-response and -tolerant mechanisms in soybean. Subcellular proteomics has potential to elucidate localized cellular responses and investigate communications among subcellular components during plant growth and under stress stimuli. Furthermore, post-translational modifications play important roles in stress response and tolerance to flooding stress. Although many flood-response mechanisms have been reported, flood-tolerant mechanisms have not been fully clarified for soybean because of limitations in germplasm with flooding tolerance. This review provides an update on current biochemical and molecular networks involved in soybean tolerance against flooding stress, as well as recent developments in the area of functional genomics in terms of developing flood-tolerant soybeans. This work will expedite marker-assisted genetic enhancement studies in crops for developing high-yielding stress-tolerant lines or varieties under abiotic stress.

Exploring the Extracellular Macromolecular Composition of Crude Extracts of Penicillium rubens Strain 212 for Elucidation Its Mode of Action as a Biocontrol Agent

Penicillium rubens strain 212 (PO212) acts as an inducer of systemic resistance in tomato plants. The effect of crude extracellular extracts of PO212 on the soil-borne pathogen Fusarium oxysporum f. sp. lycopersici has been evaluated. Evidence of the involvement of soluble, thermo-labile, and proteinase-inactivated macromolecules present in PO212 crude extracts in the control of Fusarium vascular disease in tomato plants was found. Proteomic techniques and the availability of the access to the PO212 genome database have allowed the identification of glycosyl hydrolases, oxidases, and peptidases in these extracellular extracts. Furthermore, a bioassay-guided fractionation of PO212 crude extracellular extracts using an integrated membrane/solid phase extraction process was set up. This method enabled the separation of a PO212 crude extracellular extract of seven days of growth into four fractions of different molecular sizes and polarities: high molecular mass protein fraction >5 kDa, middle molecular mass protein fraction 5–1 kDa, low molecular mass metabolite fraction, and nutrients from culture medium (mainly glucose and minerals). The high and middle molecular mass protein fractions retained disease control activity in a way similar to that of the control extracts. Proteomic techniques have allowed the identification of nine putatively secreted proteins in the high molecular mass protein fraction matching those identified in the total crude extracts. Therefore, these enzymes are considered to be potentially responsible of the crude extracellular extract-induced resistance in tomato plants against F. oxysporum f. sp. lycopersici. Further studies are required to establish which of the identified proteins participate in the PO212’s action mode as a biocontrol agent.

Proteomic Strategies to Evaluate the Impact of Farming Conditions on Food Quality and Safety in Aquaculture Products

This review presents the primary applications of various proteomic strategies to evaluate the impact of farming conditions on food quality and safety in aquaculture products. Aquaculture is a quickly growing sector that represents 47% of total fish production. Food quality, dietary management, fish welfare, the stress response, food safety, and antibiotic resistance, which are covered by this review, are among the primary topics in which proteomic techniques and strategies are being successfully applied. The review concludes by outlining future directions and potential perspectives.

Nanoparticles: Synthesis, Morphophysiological Effects, and Proteomic Responses of Crop Plants

Plant cells are frequently challenged with a wide range of adverse environmental conditions that restrict plant growth and limit the productivity of agricultural crops. Rapid development of nanotechnology and unsystematic discharge of metal containing nanoparticles (NPs) into the environment pose a serious threat to the ecological receptors including plants. Engineered nanoparticles are synthesized by physical, chemical, biological, or hybrid methods. In addition, volcanic eruption, mechanical grinding of earthquake-generating faults in Earth’s crust, ocean spray, and ultrafine cosmic dust are the natural source of NPs in the atmosphere. Untying the nature of plant interactions with NPs is fundamental for assessing their uptake and distribution, as well as evaluating phytotoxicity. Modern mass spectrometry-based proteomic techniques allow precise identification of low abundant proteins, protein–protein interactions, and in-depth analyses of cellular signaling networks. The present review highlights current understanding of plant responses to NPs exploiting high-throughput proteomics techniques. Synthesis of NPs, their morphophysiological effects on crops, and applications of proteomic techniques, are discussed in details to comprehend the underlying mechanism of NPs stress acclimation.

Deep analysis of the USP18-dependent ISGylome and proteome unveils important roles for USP18 in tumour cell antigenicity and radiosensitivity

The deubiquitylating enzyme USP18 is a major negative regulator of the interferon (IFN) signalling cascade. IFN pathways contribute to resistance to conventional chemotherapy, radiotherapy, and immunotherapy and are often deregulated in cancer. USP18 is the predominant human protease that cleaves interferon-stimulated gene ISG15, a ubiquitin-like protein tightly regulated in the context of innate immunity, from its modified substrate proteins in vivo. In this study, using advanced proteomic techniques, we have expanded the USP18-dependent ISGylome and proteome in a chronic myeloid leukaemia (CML)-derived cell line (HAP1) treated with type I IFN. Novel ISGylation targets were characterised that modulate the sensing of innate ligands, antigen presentation and secretion of cytokines. Consequently, CML USP18-deficient cells are more antigenic, driving increased activation of cytotoxic T lymphocytes (CTLs) and are more susceptible to irradiation. Our results suggest USP18 as a pharmacological target in cancer immunotherapy and radiotherapy.

Defeating the trypanosomatid trio: proteomics of the protozoan parasites causing neglected tropical diseases

This review highlights the key roles of proteomic techniques in the study of Leishmania spp., Trypanosoma cruzi and Trypanosoma brucei parasites.