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 …

Over the last decade, a rich variety of massively parallel assays have revolutionized our
understanding of how biological sequences encode quantitative molecular phenotypes …

The regular arrangements of β-strands around a central axis in β-barrels and of α-helices in
coiled coils contrast with the irregular tertiary structures of most globular proteins, and have …

Determining the pathogenicity of genetic variants is a critical challenge, and functional
assessment is often the only option. Experimentally characterizing millions of possible …

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

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 …

Insertions and deletions (indels) enable evolution and cause disease. Due to technical
challenges, indels are left out of most mutational scans, limiting our understanding of them in …

Macrolides and ketolides comprise a family of clinically important antibiotics that inhibit
protein synthesis by binding within the exit tunnel of the bacterial ribosome. While these …

The map** from protein sequence to function is highly complex, making it challenging to
predict how sequence changes will affect a protein's behavior and properties. We present a …

Phosphatase and tensin homolog (PTEN) is a tumor suppressor frequently mutated in
diverse cancers. Germline PTEN mutations are also associated with a range of clinical …