PLAAC: a web and command-line application to identify proteins with prion-like amino acid composition

Alex K Lancaster¹, Andrew Nutter-Upham², Susan Lindquist¹, Oliver D King²

Affiliations

¹ Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, Department of Pathology, Beth Israel Deaconess Medical Center, Center for Biomedical Informatics, Harvard Medical School, 10 Shattuck Street, Boston, MA 02115, USA, Department of Biology, Howard Hughes Medical Institute, MIT, 77 Massachusetts Avenue, Cambridge, MA 02139 and Department of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, Department of Pathology, Beth Israel Deaconess Medical Center, Center for Biomedical Informatics, Harvard Medical School, 10 Shattuck Street, Boston, MA 02115, USA, Department of Biology, Howard Hughes Medical Institute, MIT, 77 Massachusetts Avenue, Cambridge, MA 02139 and Department of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, Department of Pathology, Beth Israel Deaconess Medical Center, Center for Biomedical Informatics, Harvard Medical School, 10 Shattuck Street, Boston, MA 02115, USA, Department of Biology, Howard Hughes Medical Institute, MIT, 77 Massachusetts Avenue, Cambridge, MA 02139 and Department of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
² Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, Department of Pathology, Beth Israel Deaconess Medical Center, Center for Biomedical Informatics, Harvard Medical School, 10 Shattuck Street, Boston, MA 02115, USA, Department of Biology, Howard Hughes Medical Institute, MIT, 77 Massachusetts Avenue, Cambridge, MA 02139 and Department of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.

PMID: 24825614
PMCID: PMC4147883
DOI: 10.1093/bioinformatics/btu310

PLAAC: a web and command-line application to identify proteins with prion-like amino acid composition

Alex K Lancaster et al. Bioinformatics. 2014.

. 2014 Sep 1;30(17):2501-2.

doi: 10.1093/bioinformatics/btu310. Epub 2014 May 13.

Authors

Alex K Lancaster¹, Andrew Nutter-Upham², Susan Lindquist¹, Oliver D King²

Affiliations

¹ Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, Department of Pathology, Beth Israel Deaconess Medical Center, Center for Biomedical Informatics, Harvard Medical School, 10 Shattuck Street, Boston, MA 02115, USA, Department of Biology, Howard Hughes Medical Institute, MIT, 77 Massachusetts Avenue, Cambridge, MA 02139 and Department of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, Department of Pathology, Beth Israel Deaconess Medical Center, Center for Biomedical Informatics, Harvard Medical School, 10 Shattuck Street, Boston, MA 02115, USA, Department of Biology, Howard Hughes Medical Institute, MIT, 77 Massachusetts Avenue, Cambridge, MA 02139 and Department of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, Department of Pathology, Beth Israel Deaconess Medical Center, Center for Biomedical Informatics, Harvard Medical School, 10 Shattuck Street, Boston, MA 02115, USA, Department of Biology, Howard Hughes Medical Institute, MIT, 77 Massachusetts Avenue, Cambridge, MA 02139 and Department of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
² Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, Department of Pathology, Beth Israel Deaconess Medical Center, Center for Biomedical Informatics, Harvard Medical School, 10 Shattuck Street, Boston, MA 02115, USA, Department of Biology, Howard Hughes Medical Institute, MIT, 77 Massachusetts Avenue, Cambridge, MA 02139 and Department of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.

PMID: 24825614
PMCID: PMC4147883
DOI: 10.1093/bioinformatics/btu310

Abstract

Prions are self-templating protein aggregates that stably perpetuate distinct biological states and are of keen interest to researchers in both evolutionary and biomedical science. The best understood prions are from yeast and have a prion-forming domain with strongly biased amino acid composition, most notably enriched for Q or N. PLAAC is a web application that scans protein sequences for domains with P: rion- L: ike A: mino A: cid C: omposition. Users can upload sequence files, or paste sequences directly into a textbox. PLAAC ranks the input sequences by several summary scores and allows scores along sequences to be visualized. Text output files can be downloaded for further analyses, and visualizations saved in PDF and PNG formats.

Availability and implementation: http://plaac.wi.mit.edu/. The Ruby-based web framework and the command-line software (implemented in Java, with visualization routines in R) are available at http://github.com/whitehead/plaac under the MIT license. All software can be run under OS X, Windows and Unix.

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Figures

**Fig. 1.**
Visualization outputs from PLAAC. Top: four known yeast prion proteins with each AA color-coded by its enrichment log-likelihood ratio in PrLDs (styled after the Sequence Enrichment Visualization Tool; http://jura.wi.mit.edu/cgi-bin/bio/draw_enrichment.pl), with HMM parse indicated by outer bars. Bottom: detailed visualization of the Sup35 protein, including several prion-prediction scores discussed in the main text

See this image and copyright information in PMC

References

1. Alberti S, et al. A systematic survey identifies prions and illuminates sequence features of prionogenic proteins. Cell. 2009;137:146–158. - PMC - PubMed
1. Holmes DL, et al. Heritable remodeling of yeast multicellularity by an environmentally responsive prion. Cell. 2013;153:153–165. - PMC - PubMed
1. Kim HJ, et al. Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature. 2013;495:467–473. - PMC - PubMed
1. King OD, et al. The tip of the iceberg: RNA-binding proteins with prion-like domains in neurodegenerative disease. Brain Res. 2012;1462:61–80. - PMC - PubMed
1. Newby GA, Lindquist S. Blessings in disguise: biological benefits of prion-like mechanisms. Trends Cell Biol. 2013;23:251–259. - PubMed

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PLAAC: a web and command-line application to identify proteins with prion-like amino acid composition

Affiliations

PLAAC: a web and command-line application to identify proteins with prion-like amino acid composition

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Molecular Biology Databases