Single-Cell Multiomics Analysis for Drug Discovery
Abstract
:1. Background
2. Introduction of Omics in Drug Discovery
2.1. Genomics: The Study of What Can Happen
2.2. Transcriptomics: The Study of What Appears to Be Happening
2.3. Proteomics: The Study of What Makes It Happen
2.4. Metabolomics: The Study of What Actually Happens
2.5. Lipodomics: The Study of What Actually Happens
3. The Importance of Single-Cell Multiomics and Its Impact on Drug Discovery
4. Single-Cell Technologies
4.1. Flow Cytometry
4.2. Mass Spectrometry (MS)
4.3. Mass Cytometry
4.4. IsoLight
5. Applications of Single-Cell Omics in Drug Discovery and Development
Several Examples Are Described Below
6. Conclusions
Supplementary Materials
Funding
Conflicts of Interest
References
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Key Point | Genomics | Transcriptomics | Proteomics | Metabolomics |
---|---|---|---|---|
Definition | A sub-discipline of genetics that concerns the sequencing and analysis of an organism’s genome, with a focus on the structure, function, evolution, mapping, and editing of genomes. | The study of the total RNA or mRNA present in a cell or tissue. | Analysis of the entire protein complement of a cell, tissue, or organism within a specific set of parameters. | Large-scale study of small molecules, commonly known as metabolites, within cells, bio-fluids, tissues, or organisms; the metabolome refers to their interactions within a biological system. |
Sample | Genomic DNA and RNAs from all types of tissues. | mRNAs from all types of tissues. | All types of tissues and bio-fluids; most commonly used fluid is plasma. | Bio-fluids, such as urine or plasma; tissue extract; in vitro cultures and supernatants. |
Techniques | (a) Sequencing of DNA segments that contain methylated fragments after DNA modification with sodium bisulfate or (b) Genotyping using genome-wide oligonucleotide arrays. | DNA-array for quantifying expressed genes (through mRNA levels) Another valuable tool is RNASeq, which aids in studying gene expression and identifying new RNA species. | Identification of peptides/proteins can be determined using MS/MS based strategies. MS utilizes separation techniques including gels (i.e., 2DE), chromatography, and numerous enrichment methods (e.g., antibodies, protein-tags) | The most widely used analytical tools for metabolomic studies to identify large numbers of metabolites are proton NMR (1H-NMR) spectroscopy, GC-MS, and LC-MS. Hundreds of metabolites can be separated and measured in samples of interest such as plasma, CSF, urine, or cell extracts using a diversity of commonly used metabolomics tools, such as NMR, GC-MS and LC-MS detection. |
Data processing | Bioinformatics methods (such as Annovar; Circos; DNAnexus; Galaxy; Genome Quest; Ingenuity Variant Analysis; VAAST) are used to detect association of gene(s) with disease, and genome analysis involved hierarchical clustering. | Clustering is used to identify the gene sets; then data analysis is used for gene interpretation. This method can integrate microarray data with prior knowledge on the implication of genes in biological processes (Gene spring; Feature extraction; R; Oncomine; Ingenuity Pathway Analysis, Hierarchical, DAVID Bioinformatics Resources; Panther). | Protein identification and analysis are performed by a variety of bioinformatics tools (such as Mascot; Progenesis; MaxQuant; Proteios; PEAKS CMD; PEAKS Studio; OpenMS; Predict Protein; Rosetta), which are available to researchers. Measurement (random) and systematic (bias) errors are necessary components of proteomic analysis. | To generate and interpret the metabolic profile of the sample, data generated are combined with multivariate data analysis such as partial least square, clustering, discriminant analyses (examples of metabolomic software; BioCyc –Omics Viewer; iPath; KaPPA-View; KEGG; MapMan; MetPa; Metscape; MGV; Paintomics; Pathos; Pathvisio; ProMetra). |
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Nassar, S.F.; Raddassi, K.; Wu, T. Single-Cell Multiomics Analysis for Drug Discovery. Metabolites 2021, 11, 729. https://doi.org/10.3390/metabo11110729
Nassar SF, Raddassi K, Wu T. Single-Cell Multiomics Analysis for Drug Discovery. Metabolites. 2021; 11(11):729. https://doi.org/10.3390/metabo11110729
Chicago/Turabian StyleNassar, Sam F., Khadir Raddassi, and Terence Wu. 2021. "Single-Cell Multiomics Analysis for Drug Discovery" Metabolites 11, no. 11: 729. https://doi.org/10.3390/metabo11110729