Personalized Drug Therapy: Innovative Concept Guided With Proteoformics

Su, Junwen; Yang, Lamei; Sun, Ziran; Zhan, Xianquan

doi:10.1016/j.mcpro.2024.100737

Cited by 16 publications

(6 citation statements)

References 149 publications

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“…Also, a plethora of different co-and post-translational modifications can occur during the lifetime of a protein molecule. These processes lead to the formation of numerous protein species out of a single gene, for which the term "proteoform" has been coined, encapsulating the array of molecular expressions now employed in place of previously used names such as "protein forms", "protein isoforms", "protein species", and "protein variants" [69][70][71][184][185][186][187][188][189]. A major advantage of a two-dimensional affinity-capture-separation technique is that polyclonal antibodies are ideally suited for proteoform retrieval.…”

Section: Discussion and Future Perspectivesmentioning

confidence: 99%

Human Sputum Proteomics: Advancing Non-Invasive Diagnosis of Respiratory Diseases with Enhanced Biomarker Analysis Methods

Guzman,

Guzman

2024

IJTM

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Many ailments can be diagnosed while they are asymptomatic, meaning that the patient has no signs or symptoms of a progressing disease. If caught in their initial stage of formation, these disorders can be effectively treated, leading to successful outcomes; curative therapies can halt illnesses from advancing, thus improving the quality of life and long-term survival of the patient. Still, cutting-edge upgrades in precision technologies are necessary for early, reliable, affordable, and rapid disease detection, but also vital for the well-being of people and the future of global public health. The emerging role and utility of non-invasive and repeatable diagnostic test approaches for the detection of health conditions have been exemplified by liquid biopsies based on genomic biomarkers. As such, biological fluids permit any measurable molecular indicator or signature (e.g., proteins) to provide valuable information on an individual’s wellness and/or disease. Among the bodily secretions used for non-invasive diagnostics is sputum, a complex viscous gel-like biopolymeric network that has gained growing recognition as a rich source of biomarkers of airway infections and pulmonary diseases, and serves as a determinant to reveal other illnesses. As per the World Health Organization, the burden of respiratory conditions is exacerbated by factors ranging from considerable subjection to air pollution and occupational contaminants to tobacco smoking and second-hand smoke, in addition to poor socio-economic status. Due to the likely increase in these determinants, respiratory tract ailments are on the rise, affecting the health of many individuals, in addition to putting stress on healthcare facilities and services worldwide. The aim of this study was to perform a narrative review of sputum constituents with an emphasis on proteins and glycoproteins assessed as possible biomarkers of lung and other organ diseases. A search was conducted using mucus, sputum proteomics, sputum biomarkers, and point-of-care testing as keywords employing Google, PubMed (MEDLINE), and Web of Science, selecting the most referenced and related papers of the last decade. We, therefore, highlight the need to use expectorated or induced sputum specimens as a routine sample source for testing valuable protein biomarkers to diagnose these chronic disorders, predict inflammation and disease progression, as well as monitor the effectiveness of treatments. Further, we discuss the urgent need for fast and reliable point-of-care methods to detect and quantify crucial protein biomarkers in sputum specimens, and the limitations faced when dealing with their complex matrices.

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Section: Discussion and Future Perspectivesmentioning

confidence: 99%

Human Sputum Proteomics: Advancing Non-Invasive Diagnosis of Respiratory Diseases with Enhanced Biomarker Analysis Methods

Guzman,

Guzman

2024

IJTM

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“…This critical approach will provide objective, systems-level understanding of biology, in particular coupled with a growing appreciation of genome complexity, gene regulation, epigenetics, and metabolomics. Indeed, a recent suggestion is that the field should be doing “proteoformics”—focusing on proteoforms—rather than proteomics [ 38 ]. The reader can draw the parallel to the JFK quote above, that researchers in proteomics need to focus on what is hard because it will ultimately provide the most critical, informative, and thus essential data.…”

Section: Where Things Stand and Whymentioning

confidence: 99%

Proteomics—The State of the Field: The Definition and Analysis of Proteomes Should Be Based in Reality, Not Convenience

Coorssen,

Padula

2024

Proteomes

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With growing recognition and acknowledgement of the genuine complexity of proteomes, we are finally entering the post-proteogenomic era. Routine assessment of proteomes as inferred correlates of gene sequences (i.e., canonical ‘proteins’) cannot provide the necessary critical analysis of systems-level biology that is needed to understand underlying molecular mechanisms and pathways or identify the most selective biomarkers and therapeutic targets. These critical requirements demand the analysis of proteomes at the level of proteoforms/protein species, the actual active molecular players. Currently, only highly refined integrated or integrative top-down proteomics (iTDP) enables the analytical depth necessary to provide routine, comprehensive, and quantitative proteome assessments across the widest range of proteoforms inherent to native systems. Here we provide a broad perspective of the field, taking in historical and current realities, to establish a more balanced understanding of where the field has come from (in particular during the ten years since Proteomes was launched), current issues, and how things likely need to proceed if necessary deep proteome analyses are to succeed. We base this in our firm belief that the best proteomic analyses reflect, as closely as possible, the native sample at the moment of sampling. We also seek to emphasise that this and future analytical approaches are likely best based on the broad recognition and exploitation of the complementarity of currently successful approaches. This also emphasises the need to continuously evaluate and further optimize established approaches, to avoid complacency in thinking and expectations but also to promote the critical and careful development and introduction of new approaches, most notably those that address proteoforms. Above all, we wish to emphasise that a rigorous focus on analytical quality must override current thinking that largely values analytical speed; the latter would certainly be nice, if only proteoforms could thus be effectively, routinely, and quantitatively assessed. Alas, proteomes are composed of proteoforms, not molecular species that can be amplified or that directly mirror genes (i.e., ‘canonical’). The problem is hard, and we must accept and address it as such, but the payoff in playing this longer game of rigorous deep proteome analyses is the promise of far more selective biomarkers, drug targets, and truly personalised or even individualised medicine.

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“…Considering the perturbation of protein and proteoform profiles induced by the disease, there is hope in finding disease-specific proteoforms to be used as biomarkers or drug targets. A correlation between exact proteoforms and a given disease phenotype will give us a chance to perform a proteoform-specific assay [ 84 , 85 ].…”

Section: Clinical Aspects Of Proteoformsmentioning

confidence: 99%

Puzzle of Proteoform Variety—Where Is a Key?

Naryzhny

2024

Proteomes

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One of the human proteome puzzles is an imbalance between the theoretically calculated and experimentally measured amounts of proteoforms. Considering the possibility of combinations of different post-translational modifications (PTMs), the quantity of possible proteoforms is huge. An estimation gives more than a million different proteoforms in each cell type. But, it seems that there is strict control over the production and maintenance of PTMs. Although the potential complexity of proteoforms due to PTMs is tremendous, available information indicates that only a small part of it is being implemented. As a result, a protein could have many proteoforms according to the number of modification sites, but because of different systems of personal regulation, the profile of PTMs for a given protein in each organism is slightly different.

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Personalized Drug Therapy: Innovative Concept Guided With Proteoformics

Cited by 16 publications

References 149 publications

Human Sputum Proteomics: Advancing Non-Invasive Diagnosis of Respiratory Diseases with Enhanced Biomarker Analysis Methods

Human Sputum Proteomics: Advancing Non-Invasive Diagnosis of Respiratory Diseases with Enhanced Biomarker Analysis Methods

Proteomics—The State of the Field: The Definition and Analysis of Proteomes Should Be Based in Reality, Not Convenience

Puzzle of Proteoform Variety—Where Is a Key?

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