A kinetically controlled, isothermal method for the detection of single nucleotide mismatches.

We describe an isothermal, enzyme-free method to detect single nucleotide differences between oligonucleotides of close homology. The approach exploits kinetic differences in toe-hold-mediated, nucleic acid strand-displacement reactions to detect single nucleotide polymorphisms (SNPs) with essentially "digital" precision. The theoretical underpinning, experimental analyses, predictability, and accuracy of this new method are reported. We demonstrate detection of biologically relevant SNPs and single nucleotide differences in the let-7 family of microRNAs. The method is adaptable to microarray formats, as demonstrated with on-chip detection of SNP variants involved in susceptibility to the therapeutic agents abacavir, Herceptin, and simvastatin.

Mission critical: the need for proteomics in the era of next-generation sequencing and precision medicine.

Next generation sequencing (NGS) has ignited an unprecedented pace of discovery in the biomedical sciences that is fundamentally transforming the way that we understand, diagnose and treat disease, and has motivated the belief that true precision medicine - medicine that is tailored to an individual's genetic, biochemical and exposure profile - will be a reality in the near term. With minimal sample requirement, NGS can enable the concurrent genome-wide study of genetic variations, transcriptomes, and certain epigenetic modifications. However, interrogating proteins as efficiently as DNA and RNA can be interrogated with NGS is lacking and this hampers more comprehensive views of molecular physiology and limits advances in biomedical science and precision medicine. The fact is that innovations in proteomic technologies pale in comparison to the advances in NGS, with current methodologies suffering from issues related to reproducibility, sensitivity, sample requirements, and limited multiplexing capacity. The development of proteomic technologies to overcome these limitations would fill the void in systems biology research, catalyze clinical innovations, and expedite the realization of precision medicine.