The next generation of in situ multi-omics
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A machine learning approach to leveraging electronic health records for enhanced omics analysis
Omics studies produce a large number of measurements, enabling the development, validation and interpretation of systems-level biological models. Large cohorts are required to power these complex models; yet, the cohort size remains limited due to clinical and budgetary constraints. We introduce clinical and omics multimodal analysis enhanced with transfer learning (COMET), a machine learning framework that incorporates large, observational electronic health record databases and transfer learning to improve the analysis of small datasets from omics studies. By pretraining on electronic health record data and adaptively blending both early and late fusion strategies, COMET overcomes the limitations of existing multimodal machine learning methods. Using two independent datasets, we showed that COMET improved the predictive modelling performance and biological discovery compared with the analysis of omics data with traditional methods. By incorporating electronic health record data into omics analyses, COMET enables more precise patient classifications, beyond the simplistic binary reduction to cases and controls. This framework can be broadly applied to the analysis of multimodal omics studies and reveals more powerful biological insights from limited cohort sizes.
Lung microbial-host interface through the lens of multi-omics
In recent years, our understanding of the microbial world within us has been revolutionized by the use of culture-independent techniques. The use of multi-omic approaches can now not only comprehensively characterize the microbial environment but also evaluate its functional aspects and its relationship with the host immune response. Advances in bioinformatics have enabled high throughput and in-depth analyses of transcripts, proteins and metabolites and enormously expanded our understanding of the role of the human microbiome in different conditions. Such investigations of the lower airways have specific challenges but as the field develops, new approaches will be facilitated. In this review, we focus on how integrative multi-omics can advance our understanding of the microbial environment and its effects on the host immune tone in the lungs.
Integrated proteogenomic characterization of ampullary adenocarcinoma
Ampullary adenocarcinoma (AMPAC) is a rare and heterogeneous malignancy. Here we performed a comprehensive proteogenomic analysis of 198 samples from Chinese AMPAC patients and duodenum patients. Genomic data illustrate that 4q loss causes fatty acid accumulation and cell proliferation. Proteomic analysis has revealed three distinct clusters (C-FAM, C-AD, C-CC), among which the most aggressive cluster, C-AD, is associated with the poorest prognosis and is characterized by focal adhesion. Immune clustering identifies three immune clusters and reveals that immune cluster M1 (macrophage infiltration cluster) and M3 (DC cell infiltration cluster), which exhibit a higher immune score compared to cluster M2 (CD4+ T-cell infiltration cluster), are associated with a poor prognosis due to the potential secretion of IL-6 by tumor cells and its consequential influence. This study provides a comprehensive proteogenomic analysis for seeking for better understanding and potential treatment of AMPAC.
Anthropogenic organic aerosol in Europe produced mainly through second-generation oxidation
Exposure to anthropogenic atmospheric aerosol is a major health issue, causing several million deaths per year worldwide. The oxidation of aromatic hydrocarbons from traffic and wood combustion is an important anthropogenic source of low-volatility species in secondary organic aerosol, especially in heavily polluted environments. It is not yet established whether the formation of anthropogenic secondary organic aerosol involves mainly rapid autoxidation, slower sequential oxidation steps or a combination of the two. Here we reproduced a typical urban haze in the ‘Cosmics Leaving Outdoor Droplets’ chamber at the European Organization for Nuclear Research and observed the dynamics of aromatic oxidation products during secondary organic aerosol growth on a molecular level to determine mechanisms underlying their production and removal. We demonstrate that sequential oxidation is required for substantial secondary organic aerosol formation. Second-generation oxidation decreases the products’ saturation vapour pressure by several orders of magnitude and increases the aromatic secondary organic aerosol yields from a few percent to a few tens of percent at typical atmospheric concentrations. Through regional modelling, we show that more than 70% of the exposure to anthropogenic organic aerosol in Europe arises from second-generation oxidation.
Resolving the fundamentals of the J-integral concept by multi-method in situ nanoscale stress-strain mapping
The integrity of structural materials is oftentimes defined by their resistance against catastrophic failure through dissipative plastic processes at the crack tip, commonly quantified by the J-integral concept. However, to date the experimental stress and strain fields necessary to quantify the J-integral associated with local crack propagation in its original integral form were inaccessible. Here, we present a multi-method nanoscale strain- and stress-mapping surrounding a growing crack tip in two identical miniaturized fracture specimens made from a nanocrystalline FeCrMnNiCo high-entropy alloy. The respective samples were tested in situ in a scanning electron microscope and a synchrotron X-ray nanodiffraction setup, with detailed analyzes of loading states during elastic loading, crack tip blunting and general yielding, corroborated by a detailed elastic-plastic finite element model. This complementary in situ methodology uniquely enabled a detailed quantification of the J-integral along different integration paths from experimental nanoscale stress and strain fields. We find that conventional linear-elastic and elastic-plastic models, typically used to interpret fracture phenomena, have limited applicability at micron to nanoscale distances from propagating cracks. This for the first time unravels a limit to the path-independence of the J-integral, which has significant implications in the development and assessment of modern damage-tolerant materials and microstructures.
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