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Inferring noncoding RNA families and classes by means of genome-scale structure-based clustering.

Will S, Reiche K, Hofacker IL, Stadler PF, Backofen R - PLoS Comput. Biol. (2007)

Bottom Line: We have successfully tested the LocARNA-based clustering approach on the sequences of the RFAM-seed alignments.Furthermore, we have applied it to a previously published set of 3,332 predicted structured elements in the Ciona intestinalis genome (Missal K, Rose D, Stadler PF (2005) Noncoding RNAs in Ciona intestinalis.Bioinformatics 21 (Supplement 2): i77-i78).

View Article: PubMed Central - PubMed

Affiliation: Bioinformatics Group, Institute of Computer Science, University of Freiburg, Freiburg, Germany.

ABSTRACT
The RFAM database defines families of ncRNAs by means of sequence similarities that are sufficient to establish homology. In some cases, such as microRNAs and box H/ACA snoRNAs, functional commonalities define classes of RNAs that are characterized by structural similarities, and typically consist of multiple RNA families. Recent advances in high-throughput transcriptomics and comparative genomics have produced very large sets of putative noncoding RNAs and regulatory RNA signals. For many of them, evidence for stabilizing selection acting on their secondary structures has been derived, and at least approximate models of their structures have been computed. The overwhelming majority of these hypothetical RNAs cannot be assigned to established families or classes. We present here a structure-based clustering approach that is capable of extracting putative RNA classes from genome-wide surveys for structured RNAs. The LocARNA (local alignment of RNA) tool implements a novel variant of the Sankoff algorithm that is sufficiently fast to deal with several thousand candidate sequences. The method is also robust against false positive predictions, i.e., a contamination of the input data with unstructured or nonconserved sequences. We have successfully tested the LocARNA-based clustering approach on the sequences of the RFAM-seed alignments. Furthermore, we have applied it to a previously published set of 3,332 predicted structured elements in the Ciona intestinalis genome (Missal K, Rose D, Stadler PF (2005) Noncoding RNAs in Ciona intestinalis. Bioinformatics 21 (Supplement 2): i77-i78). In addition to recovering, e.g., tRNAs as a structure-based class, the method identifies several RNA families, including microRNA and snoRNA candidates, and suggests several novel classes of ncRNAs for which to date no representative has been experimentally characterized.

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Cluster 1384 Groups Sequences with a Well-Conserved Secondary Structure Consisting of Three Stem LoopsWhereas the sequence identity is low, we observe a high structural conservation. N, number of sequences in cluster.
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pcbi-0030065-g006: Cluster 1384 Groups Sequences with a Well-Conserved Secondary Structure Consisting of Three Stem LoopsWhereas the sequence identity is low, we observe a high structural conservation. N, number of sequences in cluster.

Mentions: The WPGMA tree contains 3,332 putative ncRNAs. A few large, prominent clusters are indicated. Among them are tRNAs and U3 snRNA, and an miRNA cluster, Figure 5, which contains the known miRNAs mir-124-a/b and let-7 as well as candidates for mir-126 and mir-7. Clusters 1384 in Figure 6 and 249 in Figure 7 are good candidates for novel ncRNA classes. sc01 and sc03 are both example clusters based on high sequence similarity.


Inferring noncoding RNA families and classes by means of genome-scale structure-based clustering.

Will S, Reiche K, Hofacker IL, Stadler PF, Backofen R - PLoS Comput. Biol. (2007)

Cluster 1384 Groups Sequences with a Well-Conserved Secondary Structure Consisting of Three Stem LoopsWhereas the sequence identity is low, we observe a high structural conservation. N, number of sequences in cluster.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1851984&req=5

pcbi-0030065-g006: Cluster 1384 Groups Sequences with a Well-Conserved Secondary Structure Consisting of Three Stem LoopsWhereas the sequence identity is low, we observe a high structural conservation. N, number of sequences in cluster.
Mentions: The WPGMA tree contains 3,332 putative ncRNAs. A few large, prominent clusters are indicated. Among them are tRNAs and U3 snRNA, and an miRNA cluster, Figure 5, which contains the known miRNAs mir-124-a/b and let-7 as well as candidates for mir-126 and mir-7. Clusters 1384 in Figure 6 and 249 in Figure 7 are good candidates for novel ncRNA classes. sc01 and sc03 are both example clusters based on high sequence similarity.

Bottom Line: We have successfully tested the LocARNA-based clustering approach on the sequences of the RFAM-seed alignments.Furthermore, we have applied it to a previously published set of 3,332 predicted structured elements in the Ciona intestinalis genome (Missal K, Rose D, Stadler PF (2005) Noncoding RNAs in Ciona intestinalis.Bioinformatics 21 (Supplement 2): i77-i78).

View Article: PubMed Central - PubMed

Affiliation: Bioinformatics Group, Institute of Computer Science, University of Freiburg, Freiburg, Germany.

ABSTRACT
The RFAM database defines families of ncRNAs by means of sequence similarities that are sufficient to establish homology. In some cases, such as microRNAs and box H/ACA snoRNAs, functional commonalities define classes of RNAs that are characterized by structural similarities, and typically consist of multiple RNA families. Recent advances in high-throughput transcriptomics and comparative genomics have produced very large sets of putative noncoding RNAs and regulatory RNA signals. For many of them, evidence for stabilizing selection acting on their secondary structures has been derived, and at least approximate models of their structures have been computed. The overwhelming majority of these hypothetical RNAs cannot be assigned to established families or classes. We present here a structure-based clustering approach that is capable of extracting putative RNA classes from genome-wide surveys for structured RNAs. The LocARNA (local alignment of RNA) tool implements a novel variant of the Sankoff algorithm that is sufficiently fast to deal with several thousand candidate sequences. The method is also robust against false positive predictions, i.e., a contamination of the input data with unstructured or nonconserved sequences. We have successfully tested the LocARNA-based clustering approach on the sequences of the RFAM-seed alignments. Furthermore, we have applied it to a previously published set of 3,332 predicted structured elements in the Ciona intestinalis genome (Missal K, Rose D, Stadler PF (2005) Noncoding RNAs in Ciona intestinalis. Bioinformatics 21 (Supplement 2): i77-i78). In addition to recovering, e.g., tRNAs as a structure-based class, the method identifies several RNA families, including microRNA and snoRNA candidates, and suggests several novel classes of ncRNAs for which to date no representative has been experimentally characterized.

Show MeSH
Related in: MedlinePlus