Molecular Diagnostics: A Revolution in Progress

[摘要] Carl T. WittwerMolecular diagnostics now provides most laboratory tests in infectious disease and genetics, and an increasing number in oncology. Massively parallel methods allow sequencing of entire genomes, and sequence databases within and between species provide the information necessary to develop sensitive and specific diagnostic assays. Indeed, most microorganisms today are classified on the basis of sequence rather than phenotype. If a microbial sequence is present where it should not be, a presumptive diagnosis is made. Modern genetics, empowered by the 3.08 billion–base book of the human genome, has advanced beyond single-gene disorders to gene families, exomes, transcriptomes, and ultimately, to the complete genome. Severe challenges in data processing and interpretation remain, but the enormity and potential closure of the undertaking is inspiring. New classes of nucleic acid biomarkers, including long noncoding RNAs and microRNAs, provide a deep well for correlation to disease. If a patient's sequence variation is consistently associated with disease, a genetic diagnosis is made. Similarly, cancer is caused by genome sequence variations. These variations are typically widespread, with myriad copy number and sequence changes throughout the genome. Some of these variants identify molecular pathways that can be blocked or enhanced by drugs that affect tumor growth.Y.M. Dennis LoMolecular diagnostics is empowered by continual advancements in technology. Applications of massively parallel sequencing have exploded, affecting all areas of medicine, including molecular diagnostics. The polymerase chain reaction has evolved from gel analysis to real-time PCR to, most recently, digital PCR, where individual targets are amplified in picoliter to nanoliter volumes and statistics are used to calculate target concentrations instead of standard curves or internal controls. Genome-wide studies are no longer considered fishing expeditions, and disease association studies that use expression, single …

[学科分类] 过敏症与临床免疫学