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Journal ArticleDOI

pLogo: a probabilistic approach to visualizing sequence motifs

01 Dec 2013-Nature Methods (Nat Methods)-Vol. 10, Iss: 12, pp 1211-1212
TL;DR: The pLogo is described, a motif visualization in which residue heights are scaled relative to their statistical significance, in which real-time conditional probability calculations and visualizations are supported.
Abstract: Methods for visualizing protein or nucleic acid motifs have traditionally relied upon residue frequencies to graphically scale character heights. We describe the pLogo, a motif visualization in which residue heights are scaled relative to their statistical significance. A pLogo generation tool is publicly available at http://plogo.uconn.edu/ and supports real-time conditional probability calculations and visualizations.
Citations
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Journal ArticleDOI
TL;DR: It is proposed that APOBEC3A-mediated mutagenesis is much more frequent because APOBec3A itself is highly proficient at generating DNA breaks, whose repair can trigger the formation of single-strand hypermutation substrates.
Abstract: Elucidation of mutagenic processes shaping cancer genomes is a fundamental problem whose solution promises insights into new treatment, diagnostic and prevention strategies. Single-strand DNA-specific APOBEC cytidine deaminase(s) are major source(s) of mutation in several cancer types. Previous indirect evidence implicated APOBEC3B as the more likely major mutator deaminase, whereas the role of APOBEC3A is not established. Using yeast models enabling the controlled generation of long single-strand genomic DNA substrates, we show that the mutation signatures of APOBEC3A and APOBEC3B are statistically distinguishable. We then apply three complementary approaches to identify cancer samples with mutation signatures resembling either APOBEC. Strikingly, APOBEC3A-like samples have over tenfold more APOBEC-signature mutations than APOBEC3B-like samples. We propose that APOBEC3A-mediated mutagenesis is much more frequent because APOBEC3A itself is highly proficient at generating DNA breaks, whose repair can trigger the formation of single-strand hypermutation substrates.

340 citations

Journal ArticleDOI
TL;DR: A general strategy to isolate and identify phosphoproteins in extracellular vesicles from human plasma as potential markers to differentiate disease from healthy states is presented and may transform cancer screening and monitoring.
Abstract: The state of protein phosphorylation can be a key determinant of cellular physiology such as early-stage cancer, but the development of phosphoproteins in biofluids for disease diagnosis remains elusive. Here we demonstrate a strategy to isolate and identify phosphoproteins in extracellular vesicles (EVs) from human plasma as potential markers to differentiate disease from healthy states. We identified close to 10,000 unique phosphopeptides in EVs isolated from small volumes of plasma samples. Using label-free quantitative phosphoproteomics, we identified 144 phosphoproteins in plasma EVs that are significantly higher in patients diagnosed with breast cancer compared with healthy controls. Several biomarkers were validated in individual patients using paralleled reaction monitoring for targeted quantitation. This study demonstrates that the development of phosphoproteins in plasma EV as disease biomarkers is highly feasible and may transform cancer screening and monitoring.

303 citations


Cites methods from "pLogo: a probabilistic approach to ..."

  • ...All the localized phosphorylation sites and corresponding phosphoproteins were submitted to pLogo software (39) and Panther (40) to determine the phosphorylation motifs and gene ontology, respectively....

    [...]

Journal ArticleDOI
12 Jul 2017-Nature
TL;DR: The underlying principles of the CRISPR–Cas adaptation system are uncovered, including sequence determinants of spacer acquisition that are relevant for understanding both the basic biology of bacterial adaptation and its technological applications.
Abstract: DNA is an excellent medium for archiving data. Recent efforts have illustrated the potential for information storage in DNA using synthesized oligonucleotides assembled in vitro. A relatively unexplored avenue of information storage in DNA is the ability to write information into the genome of a living cell by the addition of nucleotides over time. Using the Cas1-Cas2 integrase, the CRISPR-Cas microbial immune system stores the nucleotide content of invading viruses to confer adaptive immunity. When harnessed, this system has the potential to write arbitrary information into the genome. Here we use the CRISPR-Cas system to encode the pixel values of black and white images and a short movie into the genomes of a population of living bacteria. In doing so, we push the technical limits of this information storage system and optimize strategies to minimize those limitations. We also uncover underlying principles of the CRISPR-Cas adaptation system, including sequence determinants of spacer acquisition that are relevant for understanding both the basic biology of bacterial adaptation and its technological applications. This work demonstrates that this system can capture and stably store practical amounts of real data within the genomes of populations of living cells.

270 citations

Journal ArticleDOI
TL;DR: Proteome-wide steady-state protein turnover rate measurements for the evolutionarily distant but ecologically similar yeasts, Saccharomyces cerevisiae and SchizosacCharomyces pombe, find that the half-life of most proteins is much longer than currently thought and determined to a large degree by protein synthesis and dilution due to cell division.

253 citations

Journal ArticleDOI
TL;DR: A chemoproteomic workflow to map and quantify over 1,000 S-sulfenylation sites on more than 700 proteins in intact cells suggests regulatory crosstalk between redox control and signaling pathways.
Abstract: Cysteine S-sulphenylation provides redox regulation of protein functions, but the extent of this post-translational modification in cells is unknown. Here, Yang et al. develop a method to detect hundreds of S-sulphenylation sites in cells, and show that many of them respond to a physiologically relevant redox stimulus.

211 citations

References
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Journal ArticleDOI
TL;DR: WebLogo generates sequence logos, graphical representations of the patterns within a multiple sequence alignment that provide a richer and more precise description of sequence similarity than consensus sequences and can rapidly reveal significant features of the alignment otherwise difficult to perceive.
Abstract: WebLogo generates sequence logos, graphical representations of the patterns within a multiple sequence alignment. Sequence logos provide a richer and more precise description of sequence similarity than consensus sequences and can rapidly reveal significant features of the alignment otherwise difficult to perceive. Each logo consists of stacks of letters, one stack for each position in the sequence. The overall height of each stack indicates the sequence conservation at that position (measured in bits), whereas the height of symbols within the stack reflects the relative frequency of the corresponding amino or nucleic acid at that position. WebLogo has been enhanced recently with additional features and options, to provide a convenient and highly configurable sequence logo generator. A command line interface and the complete, open WebLogo source code are available for local installation and customization.

10,721 citations

Journal ArticleDOI
TL;DR: From these 'sequence logos', one can determine not only the consensus sequence but also the relative frequency of bases and the information content at every position in a site or sequence.
Abstract: A graphical method is presented for displaying the patterns in a set of aligned sequences. The characters representing the sequence are stacked on top of each other for each position in the aligned sequences. The height of each letter is made proportional to its frequency, and the letters are sorted so the most common one is on top. The height of the entire stack is then adjusted to signify the information content of the sequences at that position. From these 'sequence logos', one can determine not only the consensus sequence but also the relative frequency of bases and the information content (measured in bits) at every position in a site or sequence. The logo displays both significant residues and subtle sequence patterns.

3,232 citations

Journal ArticleDOI
13 Mar 1987-Cell
TL;DR: It is proposed that the KDEL sequence marks proteins that are to be retained in the ER and discuss possible retention mechanisms.

2,127 citations

Journal ArticleDOI
TL;DR: Current knowledge of P-loops is discussed with the additional aim of illustrating the fascinating relationship between protein sequence, structure and function.

1,972 citations