Related Experiment Video
Updated: Apr 16, 2026

Demonstration of the Sequence Alignment to Predict Across Species Susceptibility Tool for Rapid Assessment of Protein Conservation
Published on: February 10, 2023
Improving the consistency of domain annotation within the Conserved Domain Database
Myra K Derbyshire1, Noreen R Gonzales1, Shennan Lu1
1National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bldg. 38 A, Room 5S508, 8600 Rockville Pike, Bethesda, MD 20894, USA.
Abstract:
When annotating protein sequences with the footprints of evolutionarily conserved domains, conservative score or E-value thresholds need to be applied for RPS-BLAST hits, to avoid many false positives. We notice that manual inspection and classification of hits gathered at a higher threshold can add a significant amount of valuable domain annotation. We report an automated algorithm that 'rescues' valuable borderline-scoring domain hits that are well-supported by domain architecture (DA, the sequential order of conserved domains in a protein query), including tandem repeats of domain hits reported at a more conservative threshold. This algorithm is now available as a selectable option on the public conserved domain search (CD-Search) pages. We also report on the possibility to 'suppress' domain hits close to the threshold based on a lack of well-supported DA and to implement this conservatively as an option in live conserved domain searches and for pre-computed results. Improving domain annotation consistency will in turn reduce the fraction of NR sequences with incomplete DAs.
More Related Videos
07:08Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
Published on: July 14, 2015
07:15Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
Related Concept Videos
Conservation of Protein Domains Over Different Proteins
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
Conservation of Protein Domains
Conserved Binding Sites
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Conserved Binding Sites
Multi-species Conserved Sequences
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved...
Genome Annotation and Assembly