Computational Biology and Bioinformatics in Anti-SARS-CoV-2 Drug Development
Debmalya Barh, Kenneth Lundstrom in COVID-19, 2022
These approaches constitute the next-generation computational tools and technological resources for unraveling the mechanistic pathways of viral infection [46]. Such multi-omics tools and studies can be used to prepare and guide lab-based investigations. Illustrative examples are given by the in-depth proteome analysis using mass spectrometry (MS)-based proteomics and the MS-based metabolomics [46], as various diseases are associated with distorted metabolomics, and viral infection can alter host metabolism for viral survival and reproduction [47]. The success of this combined proteomics–metabolomics approach is based on the premises that an altered biomolecule profile promotes a better understanding of the altered biological pathways, which leads to a better comprehension of the complex COVID-19 pathogenesis [48]. Among the omics-based technological platforms that can be used for finding proteome biomarkers with disease diagnosis or prognosis value are plasma/serum proteomics, nasopharyngeal swab/gargle proteomics, postmortem sample proteomics, urine proteomics, and cell line model proteomics [48].
Clinical Clues, Biochemical Indices, and Biomarkers
David J. Hackam in Necrotizing Enterocolitis, 2021
Proteomics is the study of proteins, their modifications, and interactions in biological systems. Several of the studies in Table 5.1 have utilized targeted assays of established protein analytes in blood (e.g., I-FABP, IAIP, procalcitonin) and urine (SAA, CD14, or stool, e.g., calprotectin, S100A12) whose biology is well established. These studies typically demonstrate good sensitivity but poor or low specificity, and many of the earlier studies did not report predictive values. The low specificity problem with many of these biomarkers is likely related to their established biology, which includes functions that are generalized to inflammation. To address this issue, investigators have turned to high-content platforms (proteomics via mass spectrometry) for a broader analysis of the molecular changes (proteins and peptides) that are associated with the onset or progression of NEC (21–24). The translation of these studies has been limited by the multiplex nature of the analytical panels and the need for multicenter validations. Attempts to capture clinical risk features along with molecular biomarkers have demonstrated some promise for being able to resolve the ambiguity of intermediate-risk neonates (30).
The science of biotechnology
Ronald P. Evens in Biotechnology, 2020
The proteome is the complete protein makeup in the human body. Proteomics is the study of protein structures and their properties. The proteome is more complex than the genome when we consider the greater complexity of proteins, for example, 20 amino acids versus 4 nucleic acids, and their manifold structural requirements, including the amino acid sequence, disulfide bridges, glycosylation of proteins, the complex carbohydrate structures, the amino and carboxyl ends of proteins and their variation, the isoforms of the same protein in one patient and between patients, and the 3D configuration (folding) of proteins. Proteins have a certain mass, isoelectric point, and hydrophobicity, impacting their activity. Protein function will also potentially change in several circumstances, for example, during development from the fetus to a child to an adult, in disease versus normal physiology, during inflammation versus none, and possibly have different actions at specific tissue sites. All of these different properties will require sophisticated and sensitive analytical technologies to identify and understand protein structure and function. Proteomics assists us in finding new disease targets and possible biological products for therapy.
Proteomics in support of immunotherapy: contribution to model-based precision medicine
Published in Expert Review of Proteomics, 2022
Emmanuel Nony, Philippe Moingeon
Proteomics is being used across various therapeutic areas involving a dysregulation of the immune system such as cancer, allergy, infectious diseases and autoimmune and autoinflammatory diseases, for which modulating the patient’ immunity represents a valid option to alleviate symptoms. Irrespective of the disease area, the applications of proteomics share many commonalities. The latter encompass the characterization of the pathophysiology of the disease or of the causing agent (e.g. the antigen, allergen or infectious pathogen). Improving diagnostic, understanding disease heterogeneity and developing predictive and follow-up biomarkers to stratify patients in homogeneous subgroups are also very important applications. Another use of proteomics to support therapies involving the modulation of the patient’s immune system is represented by immunoproteomics, that is the detailed characterization of dysregulated immune responses causative of the disease or elicited during treatment. Proteomics is also highly valuable for quality testing of proteins used for diagnostic or therapeutic purposes. Altogether, these methods will play an important role in the future for implementing a precision medicine approach capitalizing on an unprecedented knowledge of both the disease and the immunotherapeutic drug to offer treatments better tailored to the patient’s needs and specificities.
Proteomic profiling of carbonic anhydrase CA3 in skeletal muscle
Published in Expert Review of Proteomics, 2021
Paul Dowling, Stephen Gargan, Margit Zweyer, Hemmen Sabir, Dieter Swandulla, Kay Ohlendieck
Protein identification from one-dimensional protein bands or two-dimensional gel spots is routinely performed by generating peptide mass fingerprints (PMFs) in combination with matrix-assisted laser-desorption-ionization time-of-flight (MALDI-ToF) mass spectrometry. The MALDI-ToF technique relies on peptide mass fingerprints for protein identification, whereas approaches such as electrospray ionization mass spectrometry (ESI-MS) provide peptide sequence information, which is especially powerful when analyzing complex samples or proteins of low abundance [28]. Liquid chromatography-mass spectrometry (LC-MS) can be employed with both labeling and label-free techniques for protein quantification experiments. Isobaric tags for relative and absolute quantitation (iTRAQ) and tandem mass tag (TMT) technologies are examples of a labeling approach that utilizes isobaric reagents to label amines of peptides and proteins. One type of proteome labeling begins with stable isotope amino acid(s) being included in cell growth media or rodent feed, referred to as SILAC (stable isotope labeling by amino acids in cell culture), while mammalian systems are referred to as SILAM (stable isotope labeling in mammals) [29]. High-throughput proteomics technologies are an important consideration when profiling large numbers of samples. One such high-throughput technology is an aptamer-based proteomics platform called SOMAscan that uses single-stranded oligonucleotides to bind specific proteins and simultaneously quantify hundreds of proteins in many types of protein extracts from cells or plasma [30].
TMT-Based proteomics analysis of LPS-induced acute lung injury
Published in Experimental Lung Research, 2021
Shengsong Chen, Yi Zhang, Qingyuan Zhan
The proteome is defined as the complete set of proteins produced by the genome and thus encompasses all proteins produced by all cells with an organism.3,4 The rapid development of molecular technology, especially the rise of high-throughput proteomics technology, has provided new opportunities to identify disease biomarkers.3,4 Proteomics research can provide more biological information and reveal and explain the mechanisms of biological activities, as well as the in-depth core roles of physiological and pathological phenomena.3,4 As a discovery tool, proteomics can explore specific proteins related to diseases by comparing differences in protein expression levels and protein localization in cells, body fluids or tissues under different conditions, providing clues for the study of disease pathogenesis and identification of targets for treatment and drug development.3,4