The Role of Cardiolipin Remodeling in Mitochondrial Function and Human Diseases

Yan, Yan; Kang, Bin G.

doi:10.5539/jmbr.v2n1p1

Cited by 2 publications

(1 citation statement)

References 66 publications

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“…The diversity of cellular functions and diseases in which lipids play a role substantiates their importance and the necessity of their study. − A complete understanding of these roles requires a comprehensive accounting of the lipidome, but this has proven an elusive goal. The study of complex lipid mixtures can be done with the help of rapidly scanning tandem mass spectrometers, producing overwhelming amounts of data that, in turn, require sophisticated software for interpretation.…”

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Greazy: Open-Source Software for Automated Phospholipid Tandem Mass Spectrometry Identification

et al. 2016

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Lipid identification from data produced with high-throughput technologies is essential to the elucidation of the roles played by lipids in cellular function and disease. Software tools for identifying lipids from tandem mass (MS/MS) spectra have been developed, but they are often costly or lack the sophistication of their proteomics counterparts. We have developed Greazy, an open source tool for the automated identification of phospholipids from MS/MS spectra, that utilizes methods similar to those developed for proteomics. From user-supplied parameters, Greazy builds a phospholipid search space and associated theoretical MS/MS spectra. Experimental spectra are scored against search space lipids with similar precursor masses using a peak score based on the hypergeometric distribution and an intensity score utilizing the percentage of total ion intensity residing in matching peaks. The LipidLama component filters the results via mixture modelling and density estimation. We assess Greazy’s performance against the NIST 2014 metabolomics library, observing high accuracy in a search of multiple lipid classes. We compare Greazy/LipidLama against the commercial lipid identification software LipidSearch and show that the two platforms differ considerably in the sets of identified spectra while showing good agreement on those spectra identified by both. Lastly, we demonstrate the utility of Greazy/LipidLama with different instruments. We searched data from replicates of alveolar type 2 epithelial cells obtained with an Orbitrap and from human serum replicates generated on a Q-TOF. These findings substantiate the application of proteomics derived methods to the identification of lipids. The software is available from the ProteoWizard repository: [http://tiny.cc/bumbershoot-vc12-bin64].

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