In this Review, a group of experts in fragile X syndrome analyses why the considerable drug development effort based on robust preclinical findings describing the mechanisms underlying this neurodevelopmental disorder has failed to translate into effective treatment and offers possible solutions to improve clinical trial design and therapeutic approaches.

The contribution of genomics to drug discovery and development so far has not yet lived up to the initial high expectations. Goldstein and colleagues discuss the reasons for the limited progress and review how recent advances — particularly in oncology and rare genetic diseases — may enable precision medicine strategies to harness the therapeutic potential of genomic knowledge.

This protocol describes an experimental–computational methodology for mapping the small RNA interactome in bacteria.

This protocol describes a method for cataloging genome-wide mutations that accumulated during life or culture in single adult stem cells of different human tissues, by combining whole-genome sequencing with organoid-culture technologies.

Familial hypercholesterolaemia is a common inherited condition, but it is often diagnosed only in adulthood. Individuals with familial hypercholesterolaemia have chronic increased plasma levels of low-density lipoprotein cholesterol, which can cause early-onset cardiovascular disease.

This protocol describes a microfluidics approach for culturing liquid-biopsy-derived circulating tumor cell clusters to predict a patient's response toward various therapeutic strategies.