Single-cell genome and transcriptome sequencing investigates how genotype influences the phenotype of single cells, so as to comprehensively interpret biological inheritance and explain functional ...heterogeneity at the single-cell level. Current sample preparation technologies for simultaneous DNA and RNA sequencing of the same cell are cumbersome, expensive, and suffer from cross-contamination and limited sensitivity. Herein we describe DMF-DR-seq, a nanoliter-scale single-cell multi-omics sample preparation platform based on digital microfluidics. DMF-DR-seq integrates the major steps of single-cell isolation, DNA/RNA separation, and nucleic acid amplification in situ. The results confirm the enhanced ability of DMF-DR-seq relative to current state-of-the-art technology, with lower amplification bias, higher genome-wide coverage in DNA sequencing and better gene detection ability in RNA sequencing results. By using DMF-DR-seq, we identified the genome variation-induced abnormal transcriptome expression of single circulating tumor cells (CTCs) and cancer cells from multiple myeloma patients. The results identified potentially essential genes, known as transporters associated with antigen presentation (TAP1 and TAP2), that participate in the pathologic progress. The unique flexibility, sensitivity, and accuracy of DMF-DR-seq suggest its potential utility in deeper multi-omics analysis for inheritance mechanism study in single-cell biology.
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•A nanoliter-scale microfluidic platform for single-cell simultaneous genome and transcriptome sequencing.•Exploring the correlation of genome variation and abnormal transcriptome expression to search for essential driving genes.•Identifying TAP1 and TAP2 as potentially essential genes associated with poor prognosis in multiple myeloma.
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•Cold storage induced secondary metabolites accumulation in tomato fruit.•Cold storage affected the genes and proteins involved in secondary metabolism.•Low temperature affected the ...expression of most flavonoid biosynthesis genes.•Many ripening- and fruit quality genes were down-regulated after cold storage.
Inappropriate low temperature storage usually leads to quality deterioration of harvested tomato fruits. In this study, we performed comparative metabolome, transcriptome, and proteome analyses to comprehensively understand the effects of low temperature on metabolic changes in tomato fruit (fresh fruit, C0d; 4 °C 8 days, C8d; 4 °C 7 days and then 25 °C 1 day, C7dS1). Large amounts of secondary metabolites (including flavonoids and phenolic acids) increased after low temperature treatment. The overlap differentially accumulated metabolites in three comparative groups (C0d vs. C8d, C0d vs. C7dS1, C8d vs. C7dS1) were mainly flavonoid metabolites. A total of 1438 differentially expressed genes identified in these three comparative groups were primarily enriched in metabolic pathways and secondary metabolites biosynthesis pathways. Similarly, proteomic analysis showed that the differentially expressed proteins were enriched in the secondary metabolites biosynthesis and phenylpropanoid biosynthesis pathways. There was a strong correlation between changes in flavonoid metabolites and the expression of chalcone synthase (SlCHS), chalcone isomerase-like (SlCHIL), and coumarate 3-hydroxylase (SlC3H), which are involved in the phenylpropanoid and flavonoid biosynthesis. Additionally, seven differentially expressed MYB transcription factors were identified; SlMYB91, SlMYB106, and SlMYB70 strongly correlated with flavonoid biosynthesis structural genes after low temperature treatment. Other genes involved in fruit ripening and quality were also affected by low temperature. The data generated in this study may unravel the transcriptional regulatory network of secondary metabolism associated with low-temperature storage and provide a solid foundation for future studies.
Growing evidence has shown that Transmembrane Serine Protease 2 (TMPRSS2) not only contributes to the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, but is also closely ...associated with the incidence and progression of tumours. However, the correlation of coronavirus disease (COVID‐19) and cancers, and the prognostic value and molecular function of TMPRSS2 in various cancers have not been fully understood. In this study, the expression, genetic variations, correlated genes, immune infiltration and prognostic value of TMPRSS2 were analysed in many cancers using different bioinformatics platforms. The observed findings revealed that the expression of TMPRSS2 was considerably decreased in many tumour tissues. In the prognostic analysis, the expression of TMPRSS2 was considerably linked with the clinical consequences of the brain, blood, colorectal, breast, ovarian, lung and soft tissue cancer. In protein network analysis, we determined 27 proteins as protein partners of TMPRSS2, which can regulate the progression and prognosis of cancer mediated by TMPRSS2. Besides, a high level of TMPRSS2 was linked with immune cell infiltration in various cancers. Furthermore, according to the pathway analysis of differently expressed genes (DEGs) with TMPRSS2 in lung, breast, ovarian and colorectal cancer, 160 DEGs genes were found and were significantly enriched in respiratory system infection and tumour progression pathways. In conclusion, the findings of this study demonstrate that TMPRSS2 may be an effective biomarker and therapeutic target in various cancers in humans, and may also provide new directions for specific tumour patients to prevent SARS‐CoV‐2 infection during the COVID‐19 outbreak.
•Multi-omics technologies enable comprehensive characterization of colorectal cancer (CRC).•Spatial omics provide insights into the tumor microenvironment and cellular interactions in CRC.•Artificial ...intelligence facilitates the identification of CRC biomarkers and molecular subtypes.•Integrating multi-omics and artificial intelligence advances understanding of CRC biology and personalized therapeutic strategies.
Colorectal cancer (CRC) is a leading cause of cancer-related deaths. Recent advancements in genomic technologies and analytical approaches have revolutionized CRC research, enabling precision medicine. This review highlights the integration of multi-omics, spatial omics, and artificial intelligence (AI) in advancing precision medicine for CRC. Multi-omics approaches have uncovered molecular mechanisms driving CRC progression, while spatial omics have provided insights into the spatial heterogeneity of gene expression in CRC tissues. AI techniques have been utilized to analyze complex datasets, identify new treatment targets, and enhance diagnosis and prognosis. Despite the tumor's heterogeneity and genetic and epigenetic complexity, the fusion of multi-omics, spatial omics, and AI shows the potential to overcome these challenges and advance precision medicine in CRC. The future lies in integrating these technologies to provide deeper insights and enable personalized therapies for CRC patients.
In the era of precision medicine, digital technologies and artificial intelligence, drug discovery and development face unprecedented opportunities for product and business model innovation, ...fundamentally changing the traditional approach of how drugs are discovered, developed and marketed. Critical to this transformation is the adoption of new technologies in the drug development process, catalyzing the transition from serendipity-driven to data-driven medicine. This paradigm shift comes with a need for both translation and precision, leading to a modern Translational Precision Medicine approach to drug discovery and development. Key components of Translational Precision Medicine are multi-omics profiling, digital biomarkers, model-based data integration, artificial intelligence, biomarker-guided trial designs and patient-centric companion diagnostics. In this review, we summarize and critically discuss the potential and challenges of Translational Precision Medicine from a cross-industry perspective.
Coronavirus disease 2019 (COVID-19) is a respiratory infectious disease that seriously threatens human life. The clinical manifestations of severe COVID-19 include acute respiratory distress syndrome ...and multiple organ failure. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of COVID-19, spreads through contaminated droplets. SARS-CoV-2 particles have been detected in the saliva of COVID-19 patients, implying that the virus can infect and damage the oral cavity. The oral manifestations of COVID-19 include xerostomia and gustatory dysfunction. Numerous studies showed that the four structural proteins of SARS-CoV-2 are its potential pathogenic factors, especially the S protein, which binds to human ACE2 receptors facilitating the entry of the virus into the host cells. Usually, upon entry into the host cell, a pathogen triggers the host’s immune response. However, a mount of multi-omics and immunological analyses revealed that COVID-19 is caused by immune dysregulation. A decrease in the number and phenotypes of immune cells, IFN-1 production and excessive release of certain cytokines have also been reported. In conclusion, this review summarizes the oral manifestations of COVID-19 and multi-omics analysis of SARS-CoV-2 infection.
•Multi-omics approaches revealed the health functions of Oviductus Ranae (OR).•Metabolite, protein, and gene expression changed between rats+OR and rats-OR.•Pathway enrichment analysis highlighted ...the effect of OR on lipid-related pathways.•This study lays the groundwork for the use of OR as a tonic and medicine.
Oviductus Ranae (OR) is a well-known animal-based traditional Chinese medicine and widely consumed as a nutraceutical to optimize health. However, a current in-depth understanding of OR regulating mechanisms is lacking in the field.
Metabolomics, proteomics, and transcriptomics, were used as a multi-omics approach to comprehensively investigate the health effects of OR in rats.
Healthy rats were chosen and randomized into two groups treated with or without OR (rats+OR and rats-OR). Soaked and homogenized OR was fed to healthy rats (rats+OR) for 14 days before blood samples were collected for omics analyses. Rats in the rats-OR group were administered sterile saline instead of homogenized OR. LC-MS/MS-based targeted metabolomics including lipidomics profiling was used to survey water-soluble metabolites and organic-soluble lipids in OR and plasma samples. LC-MS-based proteomics investigated the proteins in the plasma samples, and transcriptomic analysis was performed on blood cells isolated from rats+OR and rats-OR groups. Statistical analyses including fold change (FC) and orthogonal partial least squares discrimination analysis (OPLS-DA) were done to assess the differences between the two treatment groups. Plus, pathways regarding differential metabolites including lipids, proteins, and genes were annotated through Kyoto Encyclopedia of Genes and Genomes database (KEGG), and further common pathways were searched to revealing the potential effects of OR.
The LC-MS/MS-based metabolomics detected 1300 metabolites in the water phase and 981 lipids in the organic phase of OR samples. In blood samples from rats, 1580 water-soluble metabolites and 1195 organic-soluble lipids were measured in the plasma. Among them, 199 differential compounds were found between rats+OR and rats-OR groups, with 97 out of 150 downregulated lipids in rats+OR (mainly TGs). Moreover, 125 of 782 proteins were differentially altered between the two treatment groups. Furthermore, 111 differentially expressed genes were found between the rats+OR and rats-OR groups. An integrated analysis of multi-omics data highlighted that OR affected lipid-related pathways, suggesting that OR administration may improve blood lipid levels and protect against cardiovascular and atherosclerotic diseases.
We deciphered a series of OR-induced changes in healthy rats using a multi-omics approach, which lays the groundwork for further studies on the preventative and therapeutic mechanisms of OR for various diseases.
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Asthma, a chronic respiratory disease with a global prevalence of approximately 300 million individuals, presents a significant societal and economic burden. This multifaceted syndrome exhibits ...diverse clinical phenotypes and pathogenic endotypes influenced by various factors. The advent of omics technologies has revolutionized asthma research by delving into the molecular foundation of the disease to unravel its underlying mechanisms. Omics technologies are employed to systematically screen for potential biomarkers, encompassing genes, transcripts, methylation sites, proteins, and even the microbiome components. This review provides an insightful overview of omics applications in asthma research, with a special emphasis on genetics, transcriptomics, epigenomics, and the microbiome. We explore the cutting-edge methods, discoveries, challenges, and potential future directions in the realm of asthma omics research. By integrating multi-omics and non-omics data through advanced statistical techniques, we aspire to advance precision medicine in asthma, guiding diagnosis, risk assessment, and personalized treatment strategies for this heterogeneous condition.
Animal venoms offer a valuable source of potent new drug leads, but their mechanisms of action are largely unknown. We therefore developed a novel network pharmacology approach based on multi-omics ...functional data integration to predict how stingray venom disrupts the physiological systems of target animals. We integrated 10 million transcripts from five stingray venom transcriptomes and 848,640 records from three high-content venom bioactivity datasets into a large functional data network. The network featured 216 signaling pathways, 29 of which were shared and targeted by 70 transcripts and 70 bioactivity hits. The network revealed clusters for single envenomation outcomes, such as pain, cardiotoxicity and hemorrhage. We carried out a detailed analysis of the pain cluster representing a primary envenomation symptom, revealing bibrotoxin and cholecystotoxin-like transcripts encoding pain-inducing candidate proteins in stingray venom. The cluster also suggested that such pain-inducing toxins primarily activate the inositol-3-phosphate receptor cascade, inducing intracellular calcium release. We also found strong evidence for synergistic activity among these candidates, with nerve growth factors cooperating with the most abundant translationally-controlled tumor proteins to activate pain signaling pathways. Our network pharmacology approach, here applied to stingray venom, can be used as a template for drug discovery in neglected venomous species.
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