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Rfam

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Rfam
Content
DescriptionThe Rfam database provides alignments, consensus secondary structures and covariance models for RNA families.
Data types
captured		RNA families
Organismsall
Contact
Research centerEBI
Primary citationPMID 33211869
Access
Data formatStockholm format
Websiterfam.org
Download URLFTP
Miscellaneous
LicensePublic domain
Bookmarkable
entities		yes

Rfam is a database containing information about non-coding RNA (ncRNA) families and other structured RNA elements. It is an annotated, open access database originally developed at the Wellcome Trust Sanger Institute in collaboration with Janelia Farm,[1][2][3][4] and currently hosted at the European Bioinformatics Institute.[5] Rfam is designed to be similar to the Pfam database for annotating protein families.

Unlike proteins, ncRNAs often have similar secondary structure without sharing much similarity in the primary sequence. Rfam divides ncRNAs into families based on evolution from a common ancestor. Producing multiple sequence alignments (MSA) of these families can provide insight into their structure and function, similar to the case of protein families. These MSAs become more useful with the addition of secondary structure information. Rfam researchers also contribute to Wikipedia's RNA WikiProject.[4][6]

Uses

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The Rfam database can be used for a variety of functions. For each ncRNA family, the interface allows users to: view and download multiple sequence alignments; read annotation; and examine species distribution of family members. There are also links provided to literature references and other RNA databases. Rfam also provides links to Wikipedia so that entries can be created or edited by users.

The interface at the Rfam website allows users to search ncRNAs by keyword, family name, or genome as well as to search by ncRNA sequence or EMBL accession number.[7] The database information is also available for download, installation and use using the INFERNAL software package.[8][9][10] The INFERNAL package can also be used with Rfam to annotate sequences (including complete genomes) for homologues to known ncRNAs.

Methods

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A theoretical ncRNA alignment from 6 species. Secondary structure base pairs are coloured in blocks and identified in the secondary structure consensus sequence (bottom line) by the < and > symbols.

In the database, the information of the secondary structure and the primary sequence, represented by the MSA, is combined in statistical models called profile stochastic context-free grammars (SCFGs), also known as covariance models. These are analogous to hidden Markov models used for protein family annotation in the Pfam database.[1] Each family in the database is represented by two multiple sequence alignments in Stockholm format and a SCFG.

The first MSA is the "seed" alignment. It is a hand-curated alignment that contains representative members of the ncRNA family and is annotated with structural information. This seed alignment is used to create the SCFG, which is used with the Rfam software INFERNAL to identify additional family members and add them to the alignment. A family-specific threshold value is chosen to avoid false positives.

Until release 12, Rfam used an initial BLAST filtering step because profile SCFGs were too computationally expensive. However, the latest versions of INFERNAL are fast enough[10] so that the BLAST step is no longer necessary.[11]

The second MSA is the “full” alignment, and is created as a result of a search using the covariance model against the sequence database. All detected homologs are aligned to the model, giving the automatically produced full alignment.

History

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Version 1.0 of Rfam was launched in 2003 and contained 25 ncRNA families and annotated about 50 000 ncRNA genes. In 2005, version 6.1 was released and contained 379 families annotating over 280 000 genes. In August 2012, version 11.0 contained 2208 RNA families, while the current version (14.9, released in November 2022) annotates 4108[7] families.

Major releases and publications

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  • 2003 - Rfam: an RNA family database.[1]
  • 2005 - Rfam: annotating non-coding RNAs in complete genomes.[2]
  • 2008 - The RNA WikiProject: community annotation of RNA families.[6]
  • 2008 - Rfam: updates to the RNA families database.[3]
  • 2011 - Rfam: Wikipedia, clans and the “decimal” release.[4]
  • 2012 - Rfam 11.0: 10 years of RNA families.[12]
  • 2014 - Rfam 12.0: updates to the RNA families database. [3]
  • 2017 - Rfam 13.0: shifting to a genome-centric resource for non-coding RNA families.[13]
  • 2020 - Rfam 14: expanded coverage of metagenomic, viral and microRNA families.[14]

Problems

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  1. The genomes of higher eukaryotes contain many ncRNA-derived pseudogenes and repeats. Distinguishing these non-functional copies from functional ncRNA is a formidable challenge.[2]
  2. Introns are not modeled by covariance models.

References

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  1. ^ a b c Griffiths-Jones S, Bateman A, Marshall M, Khanna A, Eddy SR (2003). "Rfam: an RNA family database". Nucleic Acids Res. 31 (1): 439–41. doi:10.1093/nar/gkg006. PMC 165453. PMID 12520045.
  2. ^ a b c Griffiths-Jones S, Moxon S, Marshall M, Khanna A, Eddy SR, Bateman A (2005). "Rfam: annotating non-coding RNAs in complete genomes". Nucleic Acids Res. 33 (Database issue): D121–4. doi:10.1093/nar/gki081. PMC 540035. PMID 15608160.
  3. ^ a b c Gardner PP, Daub J, Tate JG, et al. (October 2008). "Rfam: updates to the RNA families database". Nucleic Acids Research. 37 (Database issue): D136–D140. doi:10.1093/nar/gkn766. PMC 2686503. PMID 18953034.
  4. ^ a b c Gardner PP, Daub J, Tate J, Moore BL, Osuch IH, Griffiths-Jones S, Finn RD, Nawrocki EP, Kolbe DL, Eddy SR, Bateman A (2011). "Rfam: Wikipedia, clans and the "decimal" release". Nucleic Acids Res. 39 (Database issue): D141–5. doi:10.1093/nar/gkq1129. PMC 3013711. PMID 21062808.
  5. ^ "Moving to xfam.org". Xfam Blog. Retrieved 3 May 2014.
  6. ^ a b Daub J, Gardner PP, Tate J, Ramsköld D, Manske M, Scott WG, Weinberg Z, Griffiths-Jones S, Bateman A (December 2008). "The RNA WikiProject: community annotation of RNA families". RNA. 14 (12): 2462–4. doi:10.1261/rna.1200508. PMC 2590952. PMID 18945806.
  7. ^ a b "Rfam families". rfam.xfam.org.
  8. ^ Eddy SR, Durbin R (June 1994). "RNA sequence analysis using covariance models". Nucleic Acids Research. 22 (11): 2079–88. doi:10.1093/nar/22.11.2079. PMC 308124. PMID 8029015.
  9. ^ Eddy SR (2002). "A memory-efficient dynamic programming algorithm for optimal alignment of a sequence to an RNA secondary structure". BMC Bioinformatics. 3: 18. doi:10.1186/1471-2105-3-18. PMC 119854. PMID 12095421.
  10. ^ a b Nawrocki EP, Eddy SR (2013). "Infernal 1.1: 100-fold faster RNA homology searches". Bioinformatics. 29 (22): 2933–5. doi:10.1093/bioinformatics/btt509. PMC 3810854. PMID 24008419.
  11. ^ Nawrocki EP, Burge SW, Bateman A, Daub J, Eberhardt RY, Eddy SR, Floden EW, Gardner PP, Jones TA, Tate J, Finn RD (January 2015). "Rfam 12.0: updates to the RNA families database". Nucleic Acids Res. 43 (Database issue): D130–7. doi:10.1093/nar/gku1063. PMC 4383904. PMID 25392425.
  12. ^ Burge SW, Daub J, Eberhardt R, Tate J, Barquist L, Nawrocki EP, Eddy SR, Gardner PP, Bateman A (January 2013). "Rfam 11.0: 10 years of RNA families". Nucleic Acids Res. 41 (Database issue): D226–32. doi:10.1093/nar/gks1005. PMC 3531072. PMID 23125362.
  13. ^ Kalvari I, Argasinska J, Quinones-Olvera N, Nawrocki EP, Rivas E, Eddy SR, Bateman A, Finn RD, Petrov AI (January 2018). "Rfam 13.0: shifting to a genome-centric resource for non-coding RNA families". Nucleic Acids Res. 46 (D1): D335–D342. doi:10.1093/nar/gkx1038. PMC 5753348. PMID 29112718.
  14. ^ Kalvari I, Nawrocki EP, Ontiveros-Palacios N, Argasinska J, Lamkiewicz K, Marz M, Griffiths-Jones S, Toffano-Nioche C, Gautheret D, Weinberg Z, Rivas E, Eddy SR, Finn RD, Bateman A, Petrov AI (January 2021). "Rfam 14: expanded coverage of metagenomic, viral and microRNA families". Nucleic Acids Res. 49 (D1): D192–D200. doi:10.1093/nar/gkaa1047. PMC 7779021. PMID 33211869.
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