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De-DUFing the DUFs: Deciphering distant evolutionary relationships of Domains of Unknown Function using sensitive homology detection methods

Overview of attention for article published in Biology Direct, July 2015
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  • Above-average Attention Score compared to outputs of the same age (62nd percentile)

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2 Wikipedia pages

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Title
De-DUFing the DUFs: Deciphering distant evolutionary relationships of Domains of Unknown Function using sensitive homology detection methods
Published in
Biology Direct, July 2015
DOI 10.1186/s13062-015-0069-2
Pubmed ID
Authors

Richa Mudgal, Sankaran Sandhya, Nagasuma Chandra, Narayanaswamy Srinivasan

Abstract

In the post-genomic era where sequences are being determined at a rapid rate, we are highly reliant on computational methods for their tentative biochemical characterization. The Pfam database currently contains 3,786 families corresponding to "Domains of Unknown Function" (DUF) or "Uncharacterized Protein Family" (UPF), of which 3,087 families have no reported three-dimensional structure, constituting almost one-fourth of the known protein families in search for both structure and function. We applied a 'computational structural genomics' approach using five state-of-the-art remote similarity detection methods to detect the relationship between uncharacterized DUFs and domain families of known structures. The association with a structural domain family could serve as a start point in elucidating the function of a DUF. Amongst these five methods, searches in SCOP-NrichD database have been applied for the first time. Predictions were classified into high, medium and low- confidence based on the consensus of results from various approaches and also annotated with enzyme and Gene ontology terms. 614 uncharacterized DUFs could be associated with a known structural domain, of which high confidence predictions, involving at least four methods, were made for 54 families. These structure-function relationships for the 614 DUF families can be accessed on-line at http://proline.biochem.iisc.ernet.in/RHD_DUFS/ . For potential enzymes in this set, we assessed their compatibility with the associated fold and performed detailed structural and functional annotation by examining alignments and extent of conservation of functional residues. Detailed discussion is provided for interesting assignments for DUF3050, DUF1636, DUF1572, DUF2092 and DUF659. This study provides insights into the structure and potential function for nearly 20 % of the DUFs. Use of different computational approaches enables us to reliably recognize distant relationships, especially when they converge to a common assignment because the methods are often complementary. We observe that while pointers to the structural domain can offer the right clues to the function of a protein, recognition of its precise functional role is still 'non-trivial' with many DUF domains conserving only some of the critical residues. It is not clear whether these are functional vestiges or instances involving alternate substrates and interacting partners. This article was reviewed by Drs Eugene Koonin, Frank Eisenhaber and Srikrishna Subramanian.

Mendeley readers

The data shown below were compiled from readership statistics for 83 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
France 1 1%
South Africa 1 1%
Brazil 1 1%
Unknown 80 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 21 25%
Researcher 17 20%
Student > Master 8 10%
Professor 5 6%
Student > Bachelor 5 6%
Other 13 16%
Unknown 14 17%
Readers by discipline Count As %
Agricultural and Biological Sciences 35 42%
Biochemistry, Genetics and Molecular Biology 26 31%
Chemistry 2 2%
Computer Science 1 1%
Unspecified 1 1%
Other 2 2%
Unknown 16 19%

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 May 2019.
All research outputs
#4,687,886
of 15,055,070 outputs
Outputs from Biology Direct
#228
of 580 outputs
Outputs of similar age
#90,002
of 265,636 outputs
Outputs of similar age from Biology Direct
#5
of 7 outputs
Altmetric has tracked 15,055,070 research outputs across all sources so far. This one is in the 48th percentile – i.e., 48% of other outputs scored the same or lower than it.
So far Altmetric has tracked 580 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.8. This one has gotten more attention than average, scoring higher than 56% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 265,636 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 62% of its contemporaries.
We're also able to compare this research output to 7 others from the same source and published within six weeks on either side of this one. This one has scored higher than 2 of them.