Disease discovery and therapeutic opportunities are advanced by next-generation transcript and genome sequencing and a wide array of bioinformatics approaches. LC-MS can identify previously unknown proteins and proteins with posttranslational modifications from biological fluids or isolated mitochondria. Similarly, GC-MS can identify known or unique metabolites. The Olink protein platform is a technology that uses oligonucleotide-labeled antibodies and can measure over 1000 proteins in serum without the need for depletion. Many diseases are categorized based on phenotypic features then diagnosed using next-generation RNA or DNA sequencing. In parallel, proteomic and metabolomic analysis can identify novel targets linked with the disease. Subsequent bioinformatics analysis can curate and integrate these targets to uncover pathophysiologic pathways linked to disease and to identify putative therapeutic approaches. Sharma et al. measured more than 1000 analytes from the serum of patients with MELAS using SOMAscan, an aptamer-based assay that uses short oligonucleotides with single-protein binding affinity and LC-MS (8). The researchers identified more than 20 metabolites that also coincided with NADH redox imbalance.