SND1 binds SARS-CoV-2 negative-sense RNA and promotes viral RNA synthesis through NSP9.

Regulation of viral RNA biogenesis is fundamental to productive SARS-CoV-2 infection. To characterize host RNA-binding proteins (RBPs) involved in this process, we biochemically identified proteins bound to genomic and subgenomic SARS-CoV-2 RNAs. We find that the host protein SND1 binds the 5' end of negative-sense viral RNA and is required for SARS-CoV-2 RNA synthesis. SND1-depleted cells form smaller replication organelles and display diminished virus growth kinetics. We discover that NSP9, a viral RBP and direct SND1 interaction partner, is covalently linked to the 5' ends of positive- and negative-sense RNAs produced during infection. These linkages occur at replication-transcription initiation sites, consistent with NSP9 priming viral RNA synthesis. Mechanistically, SND1 remodels NSP9 occupancy and alters the covalent linkage of NSP9 to initiating nucleotides in viral RNA. Our findings implicate NSP9 in the initiation of SARS-CoV-2 RNA synthesis and unravel an unsuspected role of a cellular protein in orchestrating viral RNA production.

Systems analysis of human innate immunity in COVID-19.

Recent developments in sequencing technologies, the computer and data sciences, as well as increasingly high-throughput immunological measurements have made it possible to derive holistic views on pathophysiological processes of disease and treatment effects directly in humans. We and others have illustrated that incredibly predictive data for immune cell function can be generated by single cell multi-omics (SCMO) technologies and that these technologies are perfectly suited to dissect pathophysiological processes in a new disease such as COVID-19, triggered by SARS-CoV-2 infection. Systems level interrogation not only revealed the different disease endotypes, highlighted the differential dynamics in context of disease severity, and pointed towards global immune deviation across the different arms of the immune system, but was already instrumental to better define long COVID phenotypes, suggest promising biomarkers for disease and therapy outcome predictions and explains treatment responses for the widely used corticosteroids. As we identified SCMO to be the most informative technologies in the vest to better understand COVID-19, we propose to routinely include such single cell level analysis in all future clinical trials and cohorts addressing diseases with an immunological component.

Artificial intelligence-based multi-omics analysis fuels cancer precision medicine.

With biotechnological advancements, innovative omics technologies are constantly emerging that have enabled researchers to access multi-layer information from the genome, epigenome, transcriptome, proteome, metabolome, and more. A wealth of omics technologies, including bulk and single-cell omics approaches, have empowered to characterize different molecular layers at unprecedented scale and resolution, providing a holistic view of tumor behavior. Multi-omics analysis allows systematic interrogation of various molecular information at each biological layer while posing tricky challenges regarding how to extract valuable insights from the exponentially increasing amount of multi-omics data. Therefore, efficient algorithms are needed to reduce the dimensionality of the data while simultaneously dissecting the mysteries behind the complex biological processes of cancer. Artificial intelligence has demonstrated the ability to analyze complementary multi-modal data streams within the oncology realm. The coincident development of multi-omics technologies and artificial intelligence algorithms has fuelled the development of cancer precision medicine. Here, we present state-of-the-art omics technologies and outline a roadmap of multi-omics integration analysis using an artificial intelligence strategy. The advances made using artificial intelligence-based multi-omics approaches are described, especially concerning early cancer screening, diagnosis, response assessment, and prognosis prediction. Finally, we discuss the challenges faced in multi-omics analysis, along with tentative future trends in this field. With the increasing application of artificial intelligence in multi-omics analysis, we anticipate a shifting paradigm in precision medicine becoming driven by artificial intelligence-based multi-omics technologies.

The Emerging Concept of Transportome: State of the Art.

The array of ion channels and transporters expressed in cell membranes, collectively referred to as the transportome, is a complex and multifunctional molecular machinery; in particular, at the plasma membrane level it finely tunes the exchange of biomolecules and ions, acting as a functionally adaptive interface that accounts for dynamic plasticity in the response to environmental fluctuations and stressors. The transportome is responsible for the definition of membrane potential and its variations, participates in the transduction of extracellular signals, and acts as a filter for most of the substances entering and leaving the cell, thus enabling the homeostasis of many cellular parameters. For all these reasons, physiologists have long been interested in the expression and functionality of ion channels and transporters, in both physiological and pathological settings and across the different domains of life. Today, thanks to the high-throughput technologies of the postgenomic era, the omics approach to the study of the transportome is becoming increasingly popular in different areas of biomedical research, allowing for a more comprehensive, integrated, and functional perspective of this complex cellular apparatus. This article represents a first effort for a systematic review of the scientific literature on this topic. Here we provide a brief overview of all those studies, both primary and meta-analyses, that looked at the transportome as a whole, regardless of the biological problem or the models they used. A subsequent section is devoted to the methodological aspect by reviewing the most important public databases annotating ion channels and transporters, along with the tools they provide to retrieve such information. Before conclusions, limitations and future perspectives are also discussed.

High-throughput molecular assays for inclusion in personalised oncology trials - State-of-the-art and beyond.

In the last decades, the development of high-throughput molecular assays has revolutionised cancer diagnostics, paving the way for the concept of personalised cancer medicine. This progress has been driven by the introduction of such technologies through biomarker-driven oncology trials. In this review, strengths and limitations of various state-of-the-art sequencing technologies, including gene panel sequencing (DNA and RNA), whole-exome/whole-genome sequencing and whole-transcriptome sequencing, are explored, focusing on their ability to identify clinically relevant biomarkers with diagnostic, prognostic and/or predictive impact. This includes the need to assess complex biomarkers, for example microsatellite instability, tumour mutation burden and homologous recombination deficiency, to identify patients suitable for specific therapies, including immunotherapy. Furthermore, the crucial role of biomarker analysis and multidisciplinary molecular tumour boards in selecting patients for trial inclusion is discussed in relation to various trial concepts, including drug repurposing. Recognising that today's exploratory techniques will evolve into tomorrow's routine diagnostics and clinical study inclusion assays, the importance of emerging technologies for multimodal diagnostics, such as proteomics and in vivo drug sensitivity testing, is also discussed. In addition, key regulatory aspects and the importance of patient engagement in all phases of a clinical trial are described. Finally, we propose a set of recommendations for consideration when planning a new precision cancer medicine trial.

Mechanistic Insights into Cellular and Molecular Basis of Protein-Nanoplastic Interactions.

Plastic waste is ubiquitously present across the world, and its nano/sub-micron analogues (plastic nanoparticles, PNPs), raise severe environmental concerns affecting organisms' health. Considering the direct and indirect toxic implications of PNPs, their biological impacts are actively being studied; lately, with special emphasis on cellular and molecular mechanistic intricacies. Combinatorial OMICS studies identified proteins as major regulators of PNP mediated cellular toxicity via activation of oxidative enzymes and generation of ROS. Alteration of protein function by PNPs results in DNA damage, organellar dysfunction, and autophagy, thus resulting in inflammation/cell death. The molecular mechanistic basis of these cellular toxic endeavors is fine-tuned at the level of structural alterations in proteins of physiological relevance. Detailed biophysical studies on such protein-PNP interactions evidenced prominent modifications in their structural architecture and conformational energy landscape. Another essential aspect of the protein-PNP interactions includes bioenzymatic plastic degradation perspective, as the interactive units of plastics are essentially nano-sized. Combining all these attributes of protein-PNP interactions, the current review comprehensively documented the contemporary understanding of the concerned interactions in the light of cellular, molecular, kinetic/thermodynamic details. Additionally, the applicatory, economical facet of these interactions, PNP biogeochemical cycle and enzymatic advances pertaining to plastic degradation has also been discussed.

Gain-Type Aneuploidies Influence the Burden of Selective Long Non-Coding Transcripts in Colorectal Cancer.

Chromosomal instability is a hallmark of colorectal carcinogenesis and produces an accumulation of different forms of aneuploidies or broad copy number aberrations. Colorectal cancer is characterized by gain-type broad copy number aberrations, specifically in Chr20, Chr8q, Chr13 and Chr7, but their roles and mechanisms in cancer progression are not fully understood. It has been suggested that broad copy number gains might contribute to tumor development through the so-called caricature transcriptomic effect. We intend to investigate the impact of broad copy number gains on long non-coding RNAs' expression in colorectal cancer, given their well-known role in oncogenesis. The influence of such chromosomal aberrations on lncRNAs' transcriptome profile was investigated by SNP and transcriptome arrays in our series of colorectal cancer samples and cell lines. The correlation between aneuploidies and transcriptomic profiles led us to obtain a class of Over-UpT lncRNAs, which are transcripts upregulated in CRC and further overexpressed in colon tumors bearing specific chromosomal aberrations. The identified lncRNAs can contribute to a wide interaction network to establish the cancer driving effect of gain-type aneuploidies.

Unveiling the future of metabolic medicine: omics technologies driving personalized solutions for precision treatment of metabolic disorders.

Metabolic disorders are increasingly prevalent worldwide, leading to high rates of morbidity and mortality. The variety of metabolic illnesses can be addressed through personalized medicine. The goal of personalized medicine is to give doctors the ability to anticipate the best course of treatment for patients with metabolic problems. By analyzing a patient's metabolomic, proteomic, genetic profile, and clinical data, physicians can identify relevant diagnostic, and predictive biomarkers and develop treatment plans and therapy for acute and chronic metabolic diseases. To achieve this goal, real-time modeling of clinical data and multiple omics is essential to pinpoint underlying biological mechanisms, risk factors, and possibly useful data to promote early diagnosis and prevention of complex diseases. Incorporating cutting-edge technologies like artificial intelligence and machine learning is crucial for consolidating diverse forms of data, examining multiple variables, establishing databases of clinical indicators to aid decision-making, and formulating ethical protocols to address concerns. This review article aims to explore the potential of personalized medicine utilizing omics approaches for the treatment of metabolic disorders. It focuses on the recent advancements in genomics, epigenomics, proteomics, metabolomics, and nutrigenomics, emphasizing their role in revolutionizing personalized medicine.

Advances in Chemical Probing Concepts for Chemical Biology Applications.

Chemical probes allow us to identify, validate and confirm novel targets for therapeutic applications, enable the development of drug candidates, and open the way to new therapeutic strategies, vaccines and diagnostic tools.

Inoculation of wheat with Bacillus sp. wp-6 altered amino acid and flavonoid metabolism and promoted plant growth.

KEY MESSAGE: Inoculation of wheat seedling with Bacillus sp. wp-6 changed amino acid metabolism and flavonoid synthesis and promoted plant growth. Plant growth-promoting rhizobacteria (PGPR), which can reduce the use of agrochemicals, is vital for the development of sustainable agriculture. In this study, proteomics and metabolomics analyses were performed to investigate the effects of inoculation with a PGPR, Bacillus sp. wp-6, on wheat (Triticum aestivum L.) seedling growth. The results showed that inoculation with Bacillus sp. wp-6 increased shoot and root fresh weights by 19% and 18%, respectively, after 40 days. The expression levels of alpha-linolenic acid metabolism-related proteins and metabolites (lipoxygenase 2, allene oxide synthase 2, jasmonic acid, 17-hydroxylinolenic acid) and flavonoid biosynthesis-related proteins and metabolites (chalcone synthase 2 and PHC 4'-O-glucoside) were up-regulated. In addition, the expression levels of amino acid metabolism-related proteins (NADH-dependent glutamate synthase, bifunctional aspartokinase/homoserine, anthranilate synthase alpha subunit 1, and 3-phosphoshikimate 1-carboxyvinyltransferase) and metabolites (L-aspartate, L-arginine, and S-glutathionyl-L-cysteine) were also significantly up-regulated. Among them, NADH-dependent glutamate synthase and bifunctional aspartokinase/homoserine could act as regulators of nitrogen metabolism. Overall, inoculation of wheat with Bacillus sp. wp-6 altered alpha-linolenic acid metabolism, amino acid metabolism, and flavonoid synthesis and promoted wheat seedling growth. This study will deepen our understanding of the mechanism by which Bacillus sp. wp-6 promotes wheat growth using proteomics and metabolomics.

Omics Technologies Improving Breast Cancer Research and Diagnostics.

Breast cancer (BC) has yielded approximately 2.26 million new cases and has caused nearly 685,000 deaths worldwide in the last two years, making it the most common diagnosed cancer type in the world. BC is an intricate ecosystem formed by both the tumor microenvironment and malignant cells, and its heterogeneity impacts the response to treatment. Biomedical research has entered the era of massive omics data thanks to the high-throughput sequencing revolution, quick progress and widespread adoption. These technologies-liquid biopsy, transcriptomics, epigenomics, proteomics, metabolomics, pharmaco-omics and artificial intelligence imaging-could help researchers and clinicians to better understand the formation and evolution of BC. This review focuses on the findings of recent multi-omics-based research that has been applied to BC research, with an introduction to every omics technique and their applications for the different BC phenotypes, biomarkers, target therapies, diagnosis, treatment and prognosis, to provide a comprehensive overview of the possibilities of BC research.

From Recognition to Remedy: The Significance of Biomarkers in Neurodegenerative Disease Pathology.

With the inexorable aging of the global populace, neurodegenerative diseases (NDs) like Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) pose escalating challenges, which are underscored by their socioeconomic repercussions. A pivotal aspect in addressing these challenges lies in the elucidation and application of biomarkers for timely diagnosis, vigilant monitoring, and effective treatment modalities. This review delineates the quintessence of biomarkers in the realm of NDs, elucidating various classifications and their indispensable roles. Particularly, the quest for novel biomarkers in AD, transcending traditional markers in PD, and the frontier of biomarker research in ALS are scrutinized. Emergent susceptibility and trait markers herald a new era of personalized medicine, promising enhanced treatment initiation especially in cases of SOD1-ALS. The discourse extends to diagnostic and state markers, revolutionizing early detection and monitoring, alongside progression markers that unveil the trajectory of NDs, propelling forward the potential for tailored interventions. The synergy between burgeoning technologies and innovative techniques like -omics, histologic assessments, and imaging is spotlighted, underscoring their pivotal roles in biomarker discovery. Reflecting on the progress hitherto, the review underscores the exigent need for multidisciplinary collaborations to surmount the challenges ahead, accelerate biomarker discovery, and herald a new epoch of understanding and managing NDs. Through a panoramic lens, this article endeavors to provide a comprehensive insight into the burgeoning field of biomarkers in NDs, spotlighting the promise they hold in transforming the diagnostic landscape, enhancing disease management, and illuminating the pathway toward efficacious therapeutic interventions.

Mass spectrometry-based forest tree metabolomics.

Research in forest tree species has advanced slowly when compared with other agricultural crops and model organisms, mainly due to the long-life cycles, large genome sizes, and lack of genomic tools. Additionally, trees are complex matrices, and the presence of interferents (e.g., oleoresins and cellulose) challenges the analysis of tree tissues with mass spectrometry (MS)-based analytical platforms. In this review, advances in MS-based forest tree metabolomics are discussed. Given their economic and ecological significance, particular focus is given to Pinus, Quercus, and Eucalyptus forest tree species to better understand their metabolite responses to abiotic and biotic stresses in the current climate change scenario. Furthermore, MS-based metabolomics technologies produce large and complex datasets that require expertize to adequately manage, process, analyze, and store the data in dedicated repositories. To ensure that the full potential of forest tree metabolomics data are translated into new knowledge, these data should comply with the FAIR principles (i.e., Findable, Accessible, Interoperable, and Re-usable). It is essential that adequate standards are implemented to annotate metadata from forest tree metabolomics studies as is already required by many science and governmental agencies and some major scientific publishers. © 2019 John Wiley & Sons Ltd. Mass Spec Rev 40:126-157, 2021.

Metabolomics, Microbiomics, Machine learning during the COVID-19 pandemic.

COVID-19 pandemic has a significant impact worldwide, from the point of view of public health, social, and economic aspects. The correct strategies of diagnosis and global management are still under debate. In the next future, we firmly believe that combining the so-called 3 M's (metabolomics, microbiomics, and machine learning [artificial intelligence]) will be the optimal, accurate tool for the early diagnosis of COVID-19 subjects, risk assessment and stratification, patient management, and decision-making. If the currently available preliminary data obtain further confirms, through future studies on larger samples, simple biomarkers will provide predictive models for data analysis and interpretation, allowing a step toward personalized holistic medicine.

Advances in the human skin microbiota and its roles in cutaneous diseases.

Skin is the largest organ in the human body, and the interplay between the environment factors and human skin leads to some skin diseases, such as acne, psoriasis, and atopic dermatitis. As the first line of human immune defense, skin plays significant roles in human health via preventing the invasion of pathogens that is heavily influenced by the skin microbiota. Despite being a challenging niche for microbes, human skin is colonized by diverse commensal microorganisms that shape the skin environment. The skin microbiota can affect human health, and its imbalance and dysbiosis contribute to the skin diseases. This review focuses on the advances in our understanding of skin microbiota and its interaction with human skin. Moreover, the potential roles of microbiota in skin health and diseases are described, and some key species are highlighted. The prevention, diagnosis and treatment strategies for microbe-related skin diseases, such as healthy diets, lifestyles, probiotics and prebiotics, are discussed. Strategies for modulation of skin microbiota using synthetic biology are discussed as an interesting venue for optimization of the skin-microbiota interactions. In summary, this review provides insights into human skin microbiota recovery, the interactions between human skin microbiota and diseases, and the strategies for engineering/rebuilding human skin microbiota.

Physiological, proteomic, and metabolomic analysis provide insights into Bacillus sp.-mediated salt tolerance in wheat.

KEY MESSAGE: Herein, the inoculation with strain wp-6 promoted the growth of wheat seedlings by improving the energy production and conversion of wheat seedlings and alleviating salt stress. Soil salinization decreases crop productivity due to high toxicity of sodium ions to plants. Plant growth-promoting rhizobacteria (PGPR) have been demonstrated to alleviate salinity stress. However, the mechanism of PGPR in improving plant salt tolerance remains unclear. In this study, physiological analysis, proteomics, and metabolomics were applied to investigate the changes in wheat seedlings under salt stress (150 mM NaCl), both with and without plant root inoculation with wp-6 (Bacillus sp.). Under salt stress, root inoculation with strain wp-6 increased plant biomass (57%) and root length (25%). The Na+ content was reduced, while the K+ content and K+/Na+ ratio were increased. The content of malondialdehyde was decreased by 31.94% after inoculation of wp-6 under salt stress, while the content of proline, soluble sugar, and soluble protein were increased by 7.48%, 12.34%, and 4.12%, respectively. The peroxidase, catalase, and superoxide dismutase activities were increased after inoculation of wp-6 under salt stress. Galactose metabolism, phenylalanine metabolism, caffeine metabolism, ubiquinone and other terpenoid-quinone biosynthesis, and glutathione metabolism might play an important role in promoting the growth of salt-stressed wheat seedlings after the inoculation with wp-6. Interaction analysis of differentially expressed proteins and metabolites found that energy production and transformation-related proteins and six metabolites (D-arginine, palmitoleic acid, chlorophyllide b, rutin, pheophorbide a, and vanillylamine) were mainly involved in the growth of wheat seedlings after the inoculation with wp-6 under salt stress. Furthermore, correlation analysis found that inoculation with wp-6 promotes the growth of salt-stressed wheat seedlings mainly through regulating amino acid metabolism and porphyrin and chlorophyll metabolism. This study provides an eco-friendly method to increase agricultural productivity and paves a way to sustainable agriculture.

Promising Strategies for Preserving Adult Endothelium Health and Reversing Its Dysfunction: From Liquid Biopsy to New Omics Technologies and Noninvasive Circulating Biomarkers.

The endothelium has multiple functions, ranging from maintaining vascular homeostasis and providing nutrition and oxygen to tissues to evocating inflammation under adverse conditions and determining endothelial barrier disruption, resulting in dysfunction. Endothelial dysfunction represents a common condition associated with the pathogenesis of all diseases of the cardiovascular system, as well as of diseases of all of the other systems of the human body, including sepsis, acute respiratory distress syndrome, and COVID-19 respiratory distress. Such evidence is leading to the identification of potential biomarkers and therapeutic targets for preserving, reverting, or restoring endothelium integrity and functionality by promptly treating its dysfunction. Here, some strategies for achieving these goals are explored, despite the diverse challenges that exist, necessitating significant bench work associated with an increased number of clinical studies.

Contribution of -Omics Technologies in the Study of Porphyromonas gingivalis during Periodontitis Pathogenesis: A Minireview.

Periodontitis is a non-communicable chronic inflammatory disease characterized by the progressive and irreversible breakdown of the soft periodontal tissues and resorption of teeth-supporting alveolar bone. The etiology of periodontitis involves dysbiotic shifts in the diversity of microbial communities inhabiting the subgingival crevice, which is dominated by anaerobic Gram-negative bacteria, including Porphyromonas gingivalis. Indeed, P. gingivalis is a keystone pathogen with a repertoire of attributes that allow it to colonize periodontal tissues and influence the metabolism, growth rate, and virulence of other periodontal bacteria. The pathogenic potential of P. gingivalis has been traditionally analyzed using classical biochemical and molecular approaches. However, the arrival of new techniques, such as whole-genome sequencing, metagenomics, metatranscriptomics, proteomics, and metabolomics, allowed the generation of high-throughput data, offering a suitable option for bacterial analysis, allowing a deeper understanding of the pathogenic properties of P. gingivalis and its interaction with the host. In the present review, we revise the use of the different -omics technologies and techniques used to analyze bacteria and discuss their potential in studying the pathogenic potential of P. gingivalis.

Debaryomyces hansenii: an old acquaintance for a fresh start in the era of the green biotechnology.

The halophilic yeast Debaryomyces hansenii has been studied for several decades, serving as eukaryotic model for understanding salt and osmotic tolerance. Nevertheless, lack of consensus among different studies is found and, sometimes, contradictory information derived from studies performed in very diverse conditions. These two factors hampered its establishment as the key biotechnological player that was called to be in the past decade. On top of that, very limited (often deficient) engineering tools are available for this yeast. Fortunately Debaryomyces is again gaining momentum and recent advances using highly instrumented lab scale bioreactors, together with advanced -omics and HT-robotics, have revealed a new set of interesting results. Those forecast a very promising future for D. hansenii in the era of the so-called green biotechnology. Moreover, novel genetic tools enabling precise gene editing on this yeast are now available. In this review, we highlight the most recent developments, which include the identification of a novel gene implicated in salt tolerance, a newly proposed survival mechanism for D. hansenii at very high salt and limiting nutrient concentrations, and its utilization as production host in biotechnological processes.

Know when and how to die: gaining insights into the molecular regulation of leaf senescence.

Senescence is the ultimate phase in the life cycle of leaves which is crucial for recycling of nutrients to maintain plant fitness and reproductive success. The earliest visible manifestation of leaf senescence is their yellowing, which usually commences with the breakdown of chlorophyll. The degradation process involves a gradual and highly coordinated disassembly of macromolecules resulting in the accumulation of nutrients, which are subsequently mobilized from the senescing leaves to the developing organs. Leaf senescence progresses under overly tight genetic and molecular control involving a well-orchestrated and intricate network of regulators that coordinate spatio-temporally with the influence of both internal and external cues. Owing to the advancements in omics technologies, the availability of mutant resources, scalability of molecular analyses methodologies and the advanced capacity to integrate multidimensional data, our understanding of the genetic and molecular basis of leaf ageing has greatly expanded. The review provides a compilation of the multitier regulation of senescence process and the interrelation between the environment and the terminal phase of leaf development. The knowledge gained would benefit in devising the strategies for manipulation of leaf senescence process to improve crop quality and productivity.