Clinical proteomics: Promises, challenges and limitations of affinity arrays

Betzen, Christian; Alhamdani, Mohamed Saiel Saeed; Lueong, Smiths; Schröder, Christoph; Stang, Axel; Hoheisel, Jörg D.

doi:10.1002/prca.201400156

Cited by 28 publications

(19 citation statements)

References 27 publications

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“…Understanding the functional consequence of genomic variation has been challenging, and numerous approaches have been employed. Molecular technologies, including metabolomics (metabolites), transcriptomics (RNA), proteomics (proteins), and epigenomics, have been employed to interpret the functional consequence of genomic variations (14)(15)(16)(17). In particular, the diagnosis of monogenic conditions in pediatric cases has been transformed by methods that allow interrogation of biochemical and genetic data for discoveries of new associations between metabolic disorders and genes (18)(19)(20).…”

Section: Significancementioning

confidence: 99%

Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging

Hou

Martin

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Genome sequencing has established clinical utility for rare disease diagnosis. While increasing numbers of individuals have undergone elective genome sequencing, a comprehensive study surveying genome-wide disease-associated genes in adults with deep phenotyping has not been reported. Here we report the results of a 3-y precision medicine study with a goal to integrate wholegenome sequencing with deep phenotyping. A cohort of 1,190 adult participants (402 female [33.8%]; mean age, 54 y [range 20 to 89+]; 70.6% European) had whole-genome sequencing, and were deeply phenotyped using metabolomics, advanced imaging, and clinical laboratory tests in addition to family/medical history. Of 1,190 adults, 206 (17.3%) had at least 1 genetic variant with pathogenic (P) or likely pathogenic (LP) assessment that suggests a predisposition of genetic risk. A multidisciplinary clinical team reviewed all reportable findings for the assessment of genotype and phenotype associations, and 137 (11.5%) had genotype and phenotype associations. A high percentage of genotype and phenotype associations (>75%) was observed for dyslipidemia (n = 24), cardiomyopathy, arrhythmia, and other cardiac diseases (n = 42), and diabetes and endocrine diseases (n = 17). A lack of genotype and phenotype associations, a potential burden for patient care, was observed in 69 (5.8%) individuals with P/LP variants. Genomics and metabolomics associations identified 61 (5.1%) heterozygotes with phenotype manifestations affecting serum metabolite levels in amino acid, lipid and cofactor, and vitamin pathways. Our descriptive analysis provides results on the integration of whole-genome sequencing and deep phenotyping for clinical assessments in adults.genomics | advanced imaging | precision medicine | deep phenotyping | metabolomics

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Section: Significancementioning

confidence: 99%

Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging

Hou

Martin

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…Another challenge is related to the fact that proteins do not act on their own, but rather interact with other proteins, which is essential for cellular activity (Betzen et al . ).…”

Section: Molecular Biology Identification Techniques and Their Applicmentioning

confidence: 97%

“…This method also presents low sensitivity, thus leading to difficulty in detecting low-abundant proteins. Another challenge is related to the fact that proteins do not act on their own, but rather interact with other proteins, which is essential for cellular activity (Betzen et al 2015).…”

Section: The New 'Omics' Platform Technologymentioning

confidence: 99%

Application of molecular tools to elucidate the microbiota of seafood

2018

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The aim of this review is to present the methodologies currently applied to identify microbiota and pathogens transmitted to humans through seafood consumption, focusing on molecular techniques and pointing out their importance, advantages, disadvantages and applicability. Knowledge of available techniques allows researchers to identify which technique best fits their expectations. With such discernment, it will be possible to infer which disadvantages will be present and, therefore, not interfering with the final result. Two methodologies can be employed for this purpose, dependent and independent cultures. However, the dependent culture has certain limitations that can be solved through the independent cultivation techniques, such as PCR, PFGE and NGS, especially through the sequencing of the 16S rRNA region, providing a complete view of microbial diversity. These have revolutionized microbiological knowledge, mainly because they allow for the identification of uncultivable micro-organisms, which represent a substantial portion of total micro-organisms, making it possible to elucidate not yet described taxa which may display pathogenic potential, besides quantifying microbial communities, microbiota genetics, translated proteins and produced metabolites. In addition, transcriptomic and metabolomic techniques also allow for the evaluation of possible impacts that microbial communities may create in their environment, as well as the determination of potential pathogenicity to humans.

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“…Recent approaches of using longitudinal electronic health records have allowed the assessment of genetic variation in a wide range of diseases and the identification of loss of function variants in humans that improve our understanding of previously undiscovered biological functions and the development of therapeutic targets 4,8,7 . Molecular technologies, including metabolomics (metabolites), transcriptomics (RNA), proteomics (proteins), and epigenomics also have been employed to reveal the functional significance of genomic variations 15,16,17,18 . In particular, the integration of DNA sequencing with metabolomics has proven useful for discoveries of disease-associated genes and biomarkers 19,20,21 .…”

Section: Introductionmentioning

confidence: 99%

Precision Medicine Advancements Using Whole Genome Sequencing, Noninvasive Whole Body Imaging, and Functional Diagnostics

Hou

Martin

et al. 2018

Preprint

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We report the results of a three-year precision medicine study that enrolled 1190 presumed healthy participants at a single research clinic. To enable a better assessment of disease risk and improve diagnosis, a precision health platform that integrates non-invasive functional measurements and clinical tests combined with whole genome sequencing (WGS) was developed. The platform included WGS, comprehensive quantitative non-contrast whole body (WB) and brain magnetic resonance imaging/angiography (MRI/MRA), computed tomography (CT) coronary artery calcium scoring, electrocardiogram, echocardiogram, continuous cardiac monitoring, clinical laboratory tests, and metabolomics. In our cohort, 24.3% had medically significant genetic findings (MSF) which may contribute to increased risk of disease. A total of 206 unique medically significant variants in 111 genes were identified, and forty individuals (3.4%) had more than one MSF. Phenotypic testing revealed: 34.2% of our cohort had a metabolomics profile suggestive of insulin resistance, 29.2% had elevated liver fat identified by MRI, 16.4% had clinically important cardiac structure or cardiac function abnormalities on cardiac MRI or ECHO, 8.8% had a high cardiovascular risk on CT coronary artery calcium scoring (Agatston calcium score > 400, Relative Risk of 7.2), 8.0% had arrhythmia found on continuous rhythm monitoring, 6.5% had cardiac conduction disorders found on EKG, 2% had previously undetected tumors detected by WB MRI, and 2.5% had previously undetected aneurysms detected by non-contrast MRI/MRA. Using family histories, personal histories, and test results, clinical and phenotypic findings were correlated with genomic findings in 130 study participants (63.1%) with high to moderate penetrance variants, suggesting the precision health platform improves the diagnostic process in asymptomatic individuals who were at risk. Cardiovascular and endocrine diseases achieved considerable clinical associations between MSFs and clinical phenotypes (89% and 72%, respectively). These findings demonstrate the value of integrating WGS and noninvasive clinical assessments for a rapid and integrated point-of-care clinical diagnosis of age-related diseases that contribute to premature mortality.

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Clinical proteomics: Promises, challenges and limitations of affinity arrays

Cited by 28 publications

References 27 publications

Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging

Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging

Application of molecular tools to elucidate the microbiota of seafood

Precision Medicine Advancements Using Whole Genome Sequencing, Noninvasive Whole Body Imaging, and Functional Diagnostics

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