The role of the clinician in the multi‐omics era: are you ready?

Abstract

Since Garrod’s first description of alkaptonuria in 1902, and newborn screening for phenylketonuria introduced in the 1960s, P4 medicine (preventive, predictive, personalized, and participatory) has been a reality for the clinician serving patients with inherited metabolic diseases. The era of high-throughput technologies promises to accelerate its scale dramatically. Genomics, transcriptomics, epigenomics, proteomics, glycomics, metabolomics, and lipidomics offer an amazing opportunity for holistic investigation and contextual pathophysiologic understanding of inherited metabolic diseases for precise diagnosis and tailored treatment. While each of the -omics technologies is important to systems biology, some are more mature than others. Exome sequencing is emerging as a reimbursed test in clinics around the world, and untargeted metabolomics has the potential to serve as a single biochemical testing platform. The challenge lies in the integration and cautious interpretation of these big data, with translation into clinically meaningful information and/or action for our patients. A daunting but exciting task for the clinician; we provide clinical cases to illustrate the importance of his/her role as the connector between physicians, laboratory experts and researchers in the basic, computer, and clinical sciences. Open collaborations, data sharing, functional assays, and model organisms play a key role in the validation of -omics discoveries. Having all the right expertise at the table when discussing the diagnostic approach and individualized management plan according to the information yielded by -omics investigations (e.g., actionable mutations, novel therapeutic interventions), is the stepping stone of P4 medicine. Patient participation and the adjustment of the medical team’s plan to his/her and the family’s wishes most certainly is the capstone. Are you ready?

Multi-Omics Approach: New Potential Key Mechanisms Implicated in Cardiorenal Syndromes

“…The human genome comprehends 3.2 billion bases and 30,000–40,000 protein-coding genes. DNA microarrays provide a measurement of DNA sequence differences among individuals, and the expression of thousands of genes can be analyzed simultaneously [22, 23]. Transcriptomics examines genome RNA levels, both qualitatively (transcripts types, new splice sites, RNA editing sites) and quantitatively (the expressed quantity of each transcript).…”

“…Given the huge quantity of records generated in these studies, bioinformatics and statistic are fundamental for their understanding. Precise validation is important to confirm that findings are not just random results [19-22]. …”

Knowledge about Neonatal Screening among Postpartum Women and Complexity Level of Birthing Facilities

“…Since Garrod's first description of alkaptonuria in 1902 and the introduction of post-natal screening for phenylketonuria in the 1960s, preventive, predictive, personalized, and participatory (so-called "P4") medicine has been a reality for physicians who manage patients with hereditary metabolic diseases. [1] In addition to the traditional tests performed after birth, which can detect conditions difficult to identify by physical examination alone, several improved or novel prenatal and perinatal screening procedures have been developed, and major advances in neonatal diagnosis and prognosis have been achieved [2][3][4][5][6].…”

Metabolomics in the clinic: A review of the shared and unique features of untargeted metabolomics for clinical research and clinical testing

“…Small biochemicals can be defined as compounds ≤1000 m/z and include all metabolites in a biological sample—whether plasma, cerebrospinal fluid, urine, cells, or other tissue. Classes of small molecules detected by metabolomics include amino acids, carbohydrates, energy metabolites, lipids, vitamins, co‐factors, nucleotides, and xenobiotics obtained from the diet, environmental exposure, microbiota metabolism, and pharmacotherapy . Like other classes of molecules, peptides can be distinguished on metabolomics platforms.…”

“…1,2,4,7 Of the 'omics technologies, genomics was the first to be accepted in the clinical space. [20][21][22][23][24][25][26][27][28][29][30] Metabolomics, a term introduced in 1998, 31 is a relatively newer technology that has been used increasingly over the past decade ( Figure 1) and may be utilized to screen for and to identify the cause of disease.…”