Realizing the Opportunities of Genomics in Health Care

Ginsburg, Geoffrey S.

doi:10.1001/jama.2013.1465

Cited by 24 publications

(17 citation statements)

References 4 publications

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“…Indeed, whole-genome sequencing and whole-exome sequencing (WES) have been used successfully to investigate both common and rare diseases (1)(2)(3)(4)(5)(6)(7), as well as to provide guidance for drug treatment (8). Despite these successes, significant limitations remain on applying NGS in clinical settings for patient care (9)(10)(11). One of the key challenges is the proper interpretation of NGS data.…”

Section: Liningmentioning

confidence: 99%

Plasma metabolomic profiles enhance precision medicine for volunteers of normal health

Guo

Milburn

Ryals

et al. 2015

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

166

156

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Precision medicine, taking account of human individuality in genes, environment, and lifestyle for early disease diagnosis and individualized therapy, has shown great promise to transform medical care. Nontargeted metabolomics, with the ability to detect broad classes of biochemicals, can provide a comprehensive functional phenotype integrating clinical phenotypes with genetic and nongenetic factors. To test the application of metabolomics in individual diagnosis, we conducted a metabolomics analysis on plasma samples collected from 80 volunteers of normal health with complete medical records and three-generation pedigrees. Using a broadspectrum metabolomics platform consisting of liquid chromatography and GC coupled with MS, we profiled nearly 600 metabolites covering 72 biochemical pathways in all major branches of biosynthesis, catabolism, gut microbiome activities, and xenobiotics. Statistical analysis revealed a considerable range of variation and potential metabolic abnormalities across the individuals in this cohort. Examination of the convergence of metabolomics profiles with whole-exon sequences (WESs) provided an effective approach to assess and interpret clinical significance of genetic mutations, as shown in a number of cases, including fructose intolerance, xanthinuria, and carnitine deficiency. Metabolic abnormalities consistent with early indications of diabetes, liver dysfunction, and disruption of gut microbiome homeostasis were identified in several volunteers. Additionally, diverse metabolic responses to medications among the volunteers may assist to identify therapeutic effects and sensitivity to toxicity. The results of this study demonstrate that metabolomics could be an effective approach to complement next generation sequencing (NGS) for disease risk analysis, disease monitoring, and drug management in our goal toward precision care.metabolomics | whole-exome sequencing | functional phenotyping | gene penetrance | disease assessment T he rapid progression of next generation sequencing (NGS) technology in recent years has significantly reduced the cost and time required to query a patient's genome accurately. The ability to comprehensively survey genetic variations and their associations with diseases is currently central to personalized medicine and can potentially transform clinical diagnosis and disease management. Indeed, whole-genome sequencing and whole-exome sequencing (WES) have been used successfully to investigate both common and rare diseases (1-7), as well as to provide guidance for drug treatment (8). Despite these successes, significant limitations remain on applying NGS in clinical settings for patient care (9-11). One of the key challenges is the proper interpretation of NGS data. It is known that human exome sequencing identifies ∼10,000 nonsynonymous single-nucleotide variants (12). The computational algorithms and databases for predicting and prioritizing functional pathogenic variants are not yet fully effective. More importantly, the impact of nongenetic factors, such ...

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Section: Liningmentioning

confidence: 99%

Plasma metabolomic profiles enhance precision medicine for volunteers of normal health

Guo

Milburn

Ryals

et al. 2015

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

166

156

View full text Add to dashboard Cite

show abstract

“…1,2 Proponents expect that the technology will continue to improve clinical care, and early reports suggest some clinical utility in oncology and the diagnosis of rare diseases. 3,4,5 The industry, however, is in a considerable state of flux as new business models emerge, existing businesses begin to consolidate, and the industry reacts to an uncertain regulatory climate.…”

mentioning

confidence: 99%

Development of the clinical next-generation sequencing industry in a shifting policy climate

et al. 2014

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“…8-10]. Those WGS data could then be interpreted and reinterpreted by health care providers over the patient’s lifetime (or collaboratively “managed” by patients and clinicians [11]) as knowledge about the clinical relevance of genomic variants increases.…”

mentioning

confidence: 99%

“Use it or lose it” as an alternative approach to protect genetic privacy in personalized medicine

Wagner¹,

Pyeritz²

2014

Urologic Oncology: Seminars and Original Investigations

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Realizing the Opportunities of Genomics in Health Care

Cited by 24 publications

References 4 publications

Plasma metabolomic profiles enhance precision medicine for volunteers of normal health

Plasma metabolomic profiles enhance precision medicine for volunteers of normal health

Development of the clinical next-generation sequencing industry in a shifting policy climate

“Use it or lose it” as an alternative approach to protect genetic privacy in personalized medicine

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