The removal of introns from mRNA precursors and its regulation by alternative splicing are
key for eukaryotic gene expression and cellular function, as evidenced by the numerous …

Evolvability is the ability of a biological system to produce phenotypic variation that is both
heritable and adaptive. It has long been the subject of anecdotal observations and …

Many high-throughput experimental technologies have been developed to assess the
effects of large numbers of mutations (variation) on phenotypes. However, designing …

The functions of proteins and RNAs are defined by the collective interactions of many
residues, and yet most statistical models of biological sequences consider sites nearly …

Classical genetic approaches for interpreting variants, such as case-control or co-
segregation studies, require finding many individuals with each variant. Because the …

The same mutation can have different effects in different individuals. One important reason
for this is that the outcome of a mutation can depend on the genetic context in which it …

The introduction of insertion-deletions (INDELs) by non-homologous end-joining (NHEJ)
pathway underlies the mechanistic basis of CRISPR-Cas9-directed genome editing …

Multiplex assays of variant effect (MAVEs), such as deep mutational scans and massively
parallel reporter assays, test thousands of sequence variants in a single experiment. Despite …

Scalable sequence–function studies have enabled the systematic analysis and cataloging of
hundreds of thousands of coding and noncoding genetic variants in the human genome …

We describe an experimental method of three-dimensional (3D) structure determination that
exploits the increasing ease of high-throughput mutational scans. Inspired by the success of …