Detection of co-eluted peptides using database search methods

Alves, Gelio; Ogurtsov, Aleksey Y.; Kwok, Siwei; Wu, Wells W.; Wang, Guanghui; Shen, Rong-Fong; Yu, Yi‐Kuo

doi:10.1186/1745-6150-3-27

Cited by 24 publications

(14 citation statements)

References 41 publications

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“…These files contain the mass and charge of the parent ion and observed fragmentation pattern in the form of a list of m/z and intensity pairs. Once created, database search tools such as SEQUEST (3), X!Tandem (4), OMSSA (5), InsPect (6), MASCOT (7), Spectrum Mill (8), RAId_DbS (9), and others are used to analyze the .dta files to associate each MS/MS fragmentation pattern with a corresponding putative peptide sequence. Therefore, MS/MS fragmentation pattern information plays a primary role and ultimately can be used as essentially the only type of information for peptide identification in LC-MS/MS experiments (4,10).…”

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confidence: 99%

DtaRefinery, a Software Tool for Elimination of Systematic Errors from Parent Ion Mass Measurements in Tandem Mass Spectra Data Sets

Petyuk

Mayampurath

Monroe

et al. 2010

Molecular & Cellular Proteomics

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Hybrid two-stage mass spectrometers capable of both highly accurate mass measurement and high throughput MS/MS fragmentation have become widely available in recent years, allowing for significantly better discrimination between true and false MS/MS peptide identifications by the application of a relatively narrow window for maximum allowable deviations of measured parent ion masses. To fully gain the advantage of highly accurate parent ion mass measurements, it is important to limit systematic mass measurement errors. Based on our previous studies of systematic biases in mass measurement errors, here, we have designed an algorithm and software tool that eliminates the systematic errors from the peptide ion masses in MS/MS data. We demonstrate that the elimination of the systematic mass measurement errors allows for the use of tighter criteria on the deviation of measured mass from theoretical monoisotopic peptide mass, resulting in a reduction of both false discovery and false negative rates of peptide identification. A software implementation of this algorithm called DtaRefinery reads a set of fragmentation spectra, searches for MS/MS peptide identifications using a FASTA file containing expected protein sequences, fits a regression model that can estimate systematic errors, and then corrects the parent ion mass entries by removing the estimated systematic error components. The output is a new file with fragmentation spectra with updated parent ion masses. The software is freely available. Molecular & Cellular Proteomics 9: 486 -496, 2010.A key component in modern proteomics research is peptide identification through LC coupled to tandem MS where a selected parent or precursor ion from an MS scan undergoes fragmentation by collisionally activated/induced dissociation or any other methods (1). Identification of the putative peptides corresponding to the parent ions selected for fragmentation is performed by matching the observed to the theoretical MS/MS fragmentation patterns. The first step in the data analysis process is to create a set of input files representing the fragmentation spectra. For example, for the data sets from LTQ 1 FT and LTQ Orbitrap instruments, software tools such as extract_msn (part of BioWorks software package, Thermo Electron, San Jose, CA) or DeconMSn (2) are often used for this step, creating files in ".dta" or other formats for the fragmentation spectra. These files contain the mass and charge of the parent ion and observed fragmentation pattern in the form of a list of m/z and intensity pairs. Once created, database search tools such as SEQUEST (3), X!Tandem (4), OMSSA (5), InsPect (6), MASCOT (7), Spectrum Mill (8), RAId_DbS (9), and others are used to analyze the .dta files to associate each MS/MS fragmentation pattern with a corresponding putative peptide sequence. Therefore, MS/MS fragmentation pattern information plays a primary role and ultimately can be used as essentially the only type of information for peptide identification in LC-MS/MS experiments (4, 10). However, in thi...

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confidence: 99%

DtaRefinery, a Software Tool for Elimination of Systematic Errors from Parent Ion Mass Measurements in Tandem Mass Spectra Data Sets

Petyuk

Mayampurath

Monroe

et al. 2010

Molecular & Cellular Proteomics

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“…Some use the identification idea of cross‐linked peptides to identify mixed spectra 31. Others use simulated mixed spectra to study the influence of co‐eluted precursors on database and spectral library searches 32–34. These methods have shown that mixed spectra are common but less likely to result in accurate identification.…”

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confidence: 99%

pParse: A method for accurate determination of monoisotopic peaks in high‐resolution mass spectra

et al. 2011

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Determining the monoisotopic peak of a precursor is a first step in interpreting mass spectra, which is basic but non-trivial. The reason is that in the isolation window of a precursor, other peaks interfere with the determination of the monoisotopic peak, leading to wrong mass-to-charge ratio or charge state. Here we propose a method, named pParse, to export the most probable monoisotopic peaks for precursors, including co-eluted precursors. We use the relationship between the position of the highest peak and the mass of the first peak to detect candidate clusters. Then, we extract three features to sort the candidate clusters: (i) the sum of the intensity, (ii) the similarity of the experimental and the theoretical isotopic distribution, and (iii) the similarity of elution profiles. We showed that the recall of pParse, MaxQuant, and BioWorks was 98-98.8%, 0.5-17%, and 1.8-36.5% at the same precision, respectively. About 50% of tandem mass spectra are triggered by multiple precursors which are difficult to identify. Then we design a new scoring function to identify the co-eluted precursors. About 26% of all identified peptides were exclusively from co-eluted peptides. Therefore, accurately determining monoisotopic peaks, including co-eluted precursors, can greatly increase peptide identification rate.

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“…In addition, the number of cofragmented precursor ions increases along with sample complexity, further aggravating these three effects. In this context, the relation between sample complexity and peptide co‐elution and cofragmentation has been observed and described in several related studies using simulated and experimental DDA spectra . For instance, using high‐resolution MS to analyze a HeLa S3 cervix carcinoma cell lysate, Michalski et al found that more than 100,000 isotope features likely representing peptides elute in a standard LC‐MS/MS run .…”

Section: Strategies To Process Multiplexed Spectra: General Workflowsmentioning

confidence: 98%

Processing strategies and software solutions for data‐independent acquisition in mass spectrometry

et al. 2015

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Data-independent acquisition (DIA) offers several advantages over data-dependent acquisition (DDA) schemes for characterizing complex protein digests analyzed by LC-MS/MS. In contrast to the sequential detection, selection, and analysis of individual ions during DDA, DIA systematically parallelizes the fragmentation of all detectable ions within a wide m/z range regardless of intensity, thereby providing broader dynamic range of detected signals, improved reproducibility for identification, better sensitivity, and accuracy for quantification, and, potentially, enhanced proteome coverage. To fully exploit these advantages, composite or multiplexed fragment ion spectra generated by DIA require more elaborate processing algorithms compared to DDA. This review examines different DIA schemes and, in particular, discusses the concepts applied to and related to data processing. Available software implementations for identification and quantification are presented as comprehensively as possible and examples of software usage are cited. Processing workflows, including complete proprietary frameworks or combinations of modules from different open source data processing packages are described and compared in terms of software availability and usability, programming language, operating system support, input/output data formats, as well as the main principles employed in the algorithms used for identification and quantification. This comparative study concludes with further discussion of current limitations and expectable improvements in the short- and midterm future.

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Detection of co-eluted peptides using database search methods

Cited by 24 publications

References 41 publications

DtaRefinery, a Software Tool for Elimination of Systematic Errors from Parent Ion Mass Measurements in Tandem Mass Spectra Data Sets

DtaRefinery, a Software Tool for Elimination of Systematic Errors from Parent Ion Mass Measurements in Tandem Mass Spectra Data Sets

pParse: A method for accurate determination of monoisotopic peaks in high‐resolution mass spectra

Processing strategies and software solutions for data‐independent acquisition in mass spectrometry

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