The human immunopeptidome plays a central role in disease susceptibility and resistance. In our opinion, the development of immunopeptidomics and other peptide sequencing technologies should be ...prioritized during the next decade, particularly within the framework of the Human Immunopeptidome Project initiative. In this context, we present bold ideas, fresh arguments, and call upon industrial partners and funding organizations to support and champion this important initiative that we believe has the potential to save countless lives in the future.
Hot forming die quenching is used by the automotive industry to produce ultra high strength steel parts with a high strength-to-weight ratio. Crash-resistant structural parts with distributed ...properties can be obtained by controlling the local cooling rate during the quenching step using heated dies. This procedure requires detailed spatial knowledge of the heat transfer coefficient at the blank/die interface. Hot stamping experiments were conducted on Usibor® 1500P boron steel blanks to investigate how pressure and blank and die temperatures influenced the heat transfer coefficient, which was inferred using inverse heat conduction analysis. The heat transfer coefficient was found to vary throughout the experiment with deformation of the surface roughness peaks and evolution of the blank and die temperatures. Whereas the heat transfer coefficient at the beginning of the stamping process increases with the initial die temperature, it converges to a value that depends only on applied pressure. Moreover, the experimental heat transfer coefficient for zero pressure was found to match the air gap conductance predicted by semi-empirical models, but the pressure-dependent component was lower than the model-predicted solid contact conductance.
The myriad of peptides presented at the cell surface by class I and class II major histocompatibility complex (MHC) molecules are referred to as the immunopeptidome and are of great importance for ...basic and translational science. For basic science, the immunopeptidome is a critical component for understanding the immune system; for translational science, exact knowledge of the immunopeptidome can directly fuel and guide the development of next-generation vaccines and immunotherapies against autoimmunity, infectious diseases, and cancers. In this mini-review, we summarize established isolation techniques as well as emerging mass spectrometry-based platforms (i.e. SWATH-MS) to identify and quantify MHC-associated peptides. We also highlight selected biological applications and discuss important current technical limitations that need to be solved to accelerate the development of this field.
Recent theories have suggested that chronic pain could be partly maintained by maladaptive physiological responses of the organism facing a recurrent stressor. The present study examined the ...associations between basal levels of cortisol collected over seven consecutive days, the hippocampal volumes and brain activation to thermal stimulations administered in 16 patients with chronic back pain and 18 healthy control subjects. Results showed that patients with chronic back pain have higher levels of cortisol than control subjects. In these patients, higher cortisol was associated with smaller hippocampal volume and stronger pain-evoked activity in the anterior parahippocampal gyrus, a region involved in anticipatory anxiety and associative learning. Importantly, path modelling--a statistical approach used to examine the empirical validity of propositions grounded on previous literature--revealed that the cortisol levels and phasic pain responses in the parahippocampal gyrus mediated a negative association between the hippocampal volume and the chronic pain intensity. These findings support a stress model of chronic pain suggesting that the sustained endocrine stress response observed in individuals with a smaller hippocampii induces changes in the function of the hippocampal complex that may contribute to the persistent pain states.
Immunopeptidomics is a rapidly evolving field that is catalyzed by neoantigen discovery and cancer immunotherapy. Emulating the path of other omic disciplines, Vizcaíno et al. proposes that ...technological advances in the mass spectrometry field will lead to large immunopeptidomic cohort studies, and ultimately, the immunopeptidome-wide association study (IWAS) paradigm, which will provide profound insights into disease susceptibility and resistance.
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Highlights
•Immunopeptidomics bears the potential to link diseases to antigen representation.•We suggest to achieve this by analyzing the immunopeptidomes of cohorts of patients.•Current mass spectrometry-based techniques to analyze immunopeptidomes are described.•We term the proposed approach “Immunopeptidome-wide association studies” (IWAS).
The science that investigates the ensembles of all peptides associated to human leukocyte antigen (HLA) molecules is termed “immunopeptidomics” and is typically driven by mass spectrometry (MS) technologies. Recent advances in MS technologies, neoantigen discovery and cancer immunotherapy have catalyzed the launch of the Human Immunopeptidome Project (HIPP) with the goal of providing a complete map of the human immunopeptidome and making the technology so robust that it will be available in every clinic. Here, we provide a long-term perspective of the field and we use this framework to explore how we think the completion of the HIPP will truly impact the society in the future. In this context, we introduce the concept of immunopeptidome-wide association studies (IWAS). We highlight the importance of large cohort studies for the future and how applying quantitative immunopeptidomics at population scale may provide a new look at individual predisposition to common immune diseases as well as responsiveness to vaccines and immunotherapies. Through this vision, we aim to provide a fresh view of the field to stimulate new discussions within the community, and present what we see as the key challenges for the future for unlocking the full potential of immunopeptidomics in this era of precision medicine.
We present a novel mass spectrometry-based high-throughput workflow and an open-source computational and data resource to reproducibly identify and quantify HLA-associated peptides. Collectively, the ...resources support the generation of HLA allele-specific peptide assay libraries consisting of consensus fragment ion spectra, and the analysis of quantitative digital maps of HLA peptidomes generated from a range of biological sources by SWATH mass spectrometry (MS). This study represents the first community-based effort to develop a robust platform for the reproducible and quantitative measurement of the entire repertoire of peptides presented by HLA molecules, an essential step towards the design of efficient immunotherapies.
The mammalian target of rapamycin (mTOR) is a central regulator of cell growth and proliferation. mTOR signaling is frequently dysregulated in oncogenic cells, and thus an attractive target for ...anticancer therapy. Using CellDesigner, a modeling support software for graphical notation, we present herein a comprehensive map of the mTOR signaling network, which includes 964 species connected by 777 reactions. The map complies with both the systems biology markup language (SBML) and graphical notation (SBGN) for computational analysis and graphical representation, respectively. As captured in the mTOR map, we review and discuss our current understanding of the mTOR signaling network and highlight the impact of mTOR feedback and crosstalk regulations on drug‐based cancer therapy. This map is available on the Payao platform, a Web 2.0 based community‐wide interactive process for creating more accurate and information‐rich databases. Thus, this comprehensive map of the mTOR network will serve as a tool to facilitate systems‐level study of up‐to‐date mTOR network components and signaling events toward the discovery of novel regulatory processes and therapeutic strategies for cancer.
Individual differences in pain sensitivity and reactivity are well recognized but the underlying mechanisms are likely to be diverse. The phenomenon of stress-induced analgesia is well documented in ...animal research and individual variability in the stress response in humans may produce corresponding changes in pain. We assessed the magnitude of the acute stress response of 16 chronic back pain (CBP) patients and 18 healthy individuals exposed to noxious thermal stimulations administered in a functional magnetic resonance imaging experiment and tested its possible contribution to individual differences in pain perception. The temperature of the noxious stimulations was determined individually to control for differences in pain sensitivity. The two groups showed similar significant increases in reactive cortisol across the scanning session when compared with their basal levels collected over 7 consecutive days, suggesting normal hypothalamic-pituitary-adrenal axis reactivity to painful stressors in CBP patients. Critically, after controlling for any effect of group and stimulus temperature, individuals with stronger cortisol responses reported less pain unpleasantness and showed reduced blood oxygenation level-dependent activation in nucleus accumbens at the stimulus onset and in the anterior mid-cingulate cortex (aMCC), the primary somatosensory cortex, and the posterior insula. Mediation analyses indicated that pain-related activity in the aMCC mediated the relationship between the reactive cortisol response and the pain unpleasantness. Psychophysiological interaction analysis further revealed that higher stress reactivity was associated with reduced functional connectivity between the aMCC and the brainstem. These findings suggest that acute stress modulates pain in humans and contributes to individual variability in pain affect and pain-related brain activity.
Mass spectrometry is the method of choice for deep and reliable exploration of the (human) proteome. Targeted mass spectrometry reliably detects and quantifies pre-determined sets of proteins in a ...complex biological matrix and is used in studies that rely on the quantitatively accurate and reproducible measurement of proteins across multiple samples. It requires the one-time, a priori generation of a specific measurement assay for each targeted protein. SWATH-MS is a mass spectrometric method that combines data-independent acquisition (DIA) and targeted data analysis and vastly extends the throughput of proteins that can be targeted in a sample compared to selected reaction monitoring (SRM). Here we present a compendium of highly specific assays covering more than 10,000 human proteins and enabling their targeted analysis in SWATH-MS datasets acquired from research or clinical specimens. This resource supports the confident detection and quantification of 50.9% of all human proteins annotated by UniProtKB/Swiss-Prot and is therefore expected to find wide application in basic and clinical research. Data are available via ProteomeXchange (PXD000953-954) and SWATHAtlas (SAL00016-35).
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