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Recent Research Papers of Note: Jan 8, 2010

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Journal: Proteins, Feb. 1
Title: Identification, analysis, and prediction of protein ubiquitination sites
Authors: P Radivojac; V Vacic; C Haynes; RR Rocklin; A Mohan; JW Heven; MG Goebl; LM Iakoucheva

Describes the identification of 141 new ubiquitination sites using a combination of LC-MS and mutant yeast strains. "Investigation of the sequence biases and structural preferences around known ubiquitination sites indicated that their properties were similar to those of intrinsically disordered protein regions," according to the abstract. Combining new and previously known ubiquitination sites, the authors developed a random forest predictor of ubiquitination sites, UbPred. The class-balanced accuracy of UbPred reached 72 percent with the area under the ROC curve at 80 percent. "We show that gain and loss of predicted ubiquitination sites may likely represent a molecular mechanism behind a number of disease-associated mutations," the authors said.


Journal: Molecular and Cellular Proteomics, Jan. 4 [Epub ahead of print]
Title: Comparison of methods for profiling O-glycosylation: HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study of IgA1
Authors: Y Wada; A Dell; SM Haslam; B Tissot, etc.

A recent study evaluating methods used for defining N-glycan content in glycoproteins "convincingly endorsed mass spectrometry as the technique of choice for glycomic profiling in the discovery phase of diagnostic research," according to the abstract. The current paper reports the extension of the initiative's activities to assess different methods used for O-glycomic analysis. Direct MS analysis of mixtures of premethylated-reduced glycans in the positive ion mode and analysis of native reduced glycans in the negative ion mode using LC-MS approaches were found to be the most reliable strategies. Mass spectrometric methodologies to analyze O-glycopeptides were also found to be successful.


Journal: Analytical Chemistry, Jan. 1
Title: Automated platform for fractionation of human plasma glycoproteome in clinical proteomics
Authors: M Kullolli, WS Hancock; M Hincapie

Described is an automated platform consisting of targeted depletion in line with glycoprotein fractionation for studying the plasma glycoproteome. In the abstract, the authors said that a key element of the platform "is the enabling of high-throughput sample processing in a manner that minimizes analytical bias in a clinical sample set." Called High Performance Multi-Lectin Affinity Chromatography, the system comprises a serial configuration of depletion columns containing anti-albumin antibody and protein A with in-line multilectin affinity chromatography, consisting of three mixtures of lectins —concanavalin A, jacalin, and wheat germ agglutinin. The platform, the authors said, gives high recoveries for the fractionation of the plasma proteome and excellent stability. Glycoproteomes isolated using the platform "were shown to be highly reproducible and glycan specific."


Journal: Analytical Chemistry, Jan. 1
Title: Analysis of tandem mass spectra by FTMS for improved large-scale proteomics with superior protein quantification
Authors: GC McAlister; D Phanstiel; CD Wenger; MV Lee; JJ Coon

A newly developed dual-cell quadrupole linear ion trap Orbitrap hybrid mass spec was used to demonstrate the "utility of collecting high-resolution MS-MS spectral data for large-scale proteomics," according to the abstract. Compared to the older generation quadrupole linear ion trap Orbitrap, the new system produced significantly more unique peptide identifications for both resonant-excitation collision-activated dissociation and beam-type CAD, the authors said.


Journal: Journal of Proteome Research, January
Title: Artificial decoy spectral libraries for false discovery rate estimation in spectral library searching in proteomics
Authors: H Lam, EW Deutsch; R Aebersold

The authors extend a target-decoy searching strategy to spectral searching with the development and validation of a "robust method to generate realistic, but unnatural, decoy spectra," according to the abstract. The method involves random shuffling of the peptide identification of each reference spectrum in the library and "repositioning each fragment ion peak along the m/z axis to match the fragment ions expected from the shuffled sequence."


Journal: Journal of Proteome Research, January
Title: MSQuant, an open source platform for mass spectrometry-based quantitative proteomics
Authors: P Mortensen; JW Gouw; JV Olsen; SE Ong; KT Rigbolt; J Bunkenborg; J Cox; LJ Foster; AJ Heck; B Blagoev; JS Anderson; M Mann

An open-source software environment, MSQuant, is described. It allows for visualizing and validating peptide identification results directly on the raw mass spec data. By iteratively recalibrating MS data, MSQuant increases mass accuracy leading to fewer false positives, according to the authors. Algorithms to increase data quality include an MS3 score for peptide identification and a PTM score "that determines the probability that a modification such as phosphorylation is placed at a specific residue in an identified peptide," according to the abstract.


Journal: Analytical Chemistry, Dec. 22 [Epub ahead of print]
Title: Statistical analysis of peptide electron transfer dissociation fragmentation mass spectrometry
Authors: RJ Chalkley; KF Medzihradszky; AJ Lynn; PR Baker; AL Burlingame

Authors present a statistical analysis of the ion types observed from peptides produced by different enzymes. They highlight the different characteristics of electron-transfer dissociation spectra of doubly charged precursors in comparison to precursors of higher charge states.

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Journal: Journal of Proteome Research, Dec. 16 [Epub ahead of print]
Title: Comparison of extensive protein fractionation and repetitive LC-MS/MS analyses on depth of analysis for complex proteomes
Authors: H Wang; T Chang-Wong; HY Tang; DW Speicher

In the abstract, the authors said that in-depth, reproducible coverage of complex proteomes poses a challenge because of undersampling of data from LC-MS/MS analyses of tryptic digests. In the study, they used cancer cell lysates to systematically compare a GeLC-MS/MS method using four repetitive injections with a 3D method "that included solution isoelectric focusing and involved an equal number of LC-MS/MS runs," according to the abstract. The 3D method detected "substantially" more unique peptides and proteins, especially low-abundance proteins, the authors said, "demonstrating that additional fractionation at the protein level is more effective than repetitive analyses at overcoming LC-MS/MS undersampling."


Journal: Nature Biotechnology, Dec. 13 [Epub ahead of print]
Title: Label-free, normalized quantification of complex mass spectrometry data for proteomic analysis
Authors: NM Griffin; J Yu; F Long; P Oh; S Shore; Y Li; JA Koziol; JE Schnitzer

Replicate MS measurements and the use of multiple analytical methods can "expand the comprehensiveness of shotgun proteomic profiling of biological samples," according to the abstract, but inherent biases and variations in the data "create computational and statistical challenges for quantitative comparative analysis." To address this, the authors developed a normalized, label-free quantitative method, combining three MS abundance features — peptide count, spectral count, and fragment-ion intensity. The method "largely eliminated" variances between replicate MS measurements, "permitting quantitative reproducibility and highly significant quantification of thousands of proteins detected in replicate MS measurements of the same and distinct samples," and accurately predicted protein abundance more often than five other methods that were tested.


Journal: Clinical Chemistry, Dec. 10 [Epub ahead of print]
Title: Protein-based multiplex assays: Mock presubmissions to the US Food and Drug Administration
Authors: FE Regnier; SJ Skates; M Mesri; H Rodriguez; Z Tezak, etc.

Members of the NCI's Clinical Proteomics Technology Assessment for Cancer Program submitted two protein-based multiplex assay descriptions to the FDA's Office of In Vitro Diagnostic Device Evaluation and Safety in order to "evaluate the analytical measurement criteria and studies needed to validate protein-based multiplex assays," according to the abstract. Each submission described a different protein-based platform. One was a multiplex immunoaffinity mass spec platform for protein quantification, the other an immunological array platform for quantifying glycoprotein isoforms. The study, according to the authors, should help proteomics researchers identify analytical issues that need to be addressed when developing protein-based multiplex clinical assays.


Journal: Journal of Proteome Research, Dec. 9 [Epub ahead of print]
Title: An LC-IMS-MS platform providing increased dynamic range for high-throughput proteomic studies
Authors: M Belov; E Baker; EA Livesay; DJ Orton; RJ Moore; WF Danielson; DC Prior; Y Ibrahim; BL Lamarche; A Mayampurath; AA Schepmoes; DF Hopkins; K Tang; RD Smith

Authors evaluated a high-throughput approach and platform using 15-minute reversed-phase capillary liquid chromatography separations combined with ion mobility spectrometry mass spectrometry measurements. Compared to an LC-linear ion trap FTMS, their platform identified more peptides that were spiked into a tryptic digest of mouse blood plasma, the authors said in the abstract.


Journal: Journal of Proteome Research, December
Title: Quantitative serum proteomics using dual stable isotope coding and nano LC-MS/MSMS
Authors: H Wang; CH Wong; J Kennedy; Q Zhang; S Hanash

Described is a novel method for increasing the yield of quantified proteins while maintaining a high stable-isotope labeling efficacy. Intact proteins in complex biological samples are labeled with the designated dual stable isotope coding systems. Intact proteins are coded sequentially with acrylamide to label cysteine residues and with succinic anhydride to label lysine residues. Protein samples that are coded with this dual stable isotope are subjected to an online 2D-HPLC fractionation. The resolved protein fractions are digested individually with trypsin and analyzed with nano-LC-MS/MSMS.


Journal: The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society, Dec. 7 [Epub ahead of print]
Title: Proteomics out of the archive: 2-D-electrophoresis and mass spectrometry using HOPE-fixed, paraffin-embedded tissues
Authors:D Kähler; C Alexander; H Schultz; M Abdullah; D Branscheid; B Lindner; P Zabel; E Vollmer; T Goldmann

In the abstract, the authors said that proteomic analyses of paraffin-embedded tissue samples is "widely hampered by the use of formalin fixation requiring antigen retrieval procedures in molecular pathology." The Hepes-glutamic acid buffer mediated Organic solvent Protection Effect , or HOPE, technique has been demonstrated in previous studies to provide a wide range of biochemical investigations "with excellent preservation of morphologic structures, DNA, RNA, and proteins, thus supporting the multi-methodical analysis of archived specimens." Here, they show that HOPE fixation can be used for proteomic research by 2D gel and mass spectrometry using lung cancer tissues.


Journal: Proteomics, December
Title: A new generation of cross-linkers for selective detection by MALDI MS
Authors: D Paramelle; S Cantel; C Enjalbal; M Amblard; E Forest; M Heymann; C Geourion; J Martinez; G Subra

Described is a new cross-linker bearing a CHCA moiety. "The use of the CHCA-tagged cross-linker JMV 3378 in conjunction with a neutral MALDI matrix alpha-cyano-4-hydroxycinnamic methyl ester enabled specific signal enhancement in MALDI-TOF MS of cross-link containing peptides," according to the abstract.

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