Dataset Information

Artificial Intelligence Understands Peptide Observability and Assists With Absolute Protein Quantification.

ABSTRACT: Targeted mass spectrometry has become the method of choice to gain absolute quantification information of high quality, which is essential for a quantitative understanding of biological systems. However, the design of absolute protein quantification assays remains challenging due to variations in peptide observability and incomplete knowledge about factors influencing peptide detectability. Here, we present a deep learning algorithm for peptide detectability prediction, d::pPop, which allows the informed selection of synthetic proteotypic peptides for the successful design of targeted proteomics quantification assays. The deep neural network is able to learn a regression model that relates the physicochemical properties of a peptide to its ion intensity detected by mass spectrometry. The approach makes use of experimentally detected deviations from the assumed equimolar abundance of all peptides derived from a given protein. Trained on extensive proteomics datasets, d::pPop's plant and non-plant specific models can predict the quality of proteotypic peptides for not yet experimentally identified proteins. Interrogating the deep neural network after learning from ~76,000 peptides per model organism allows to investigate the impact of different physicochemical properties on the observability of a peptide, thus providing insights into peptide observability as a multifaceted process. Empirical evaluation with rank accuracy metrics showed that our prediction approach outperforms existing algorithms. We circumvent the delicate step of selecting positive and negative training sets and at the same time also more closely reflect the need for selecting the top most promising peptides for targeting a protein of interest. Further, we used an artificial QconCAT protein to experimentally validate the observability prediction. Our proteotypic peptide prediction approach not only facilitates the design of absolute protein quantification assays via a user-friendly web interface but also enables the selection of proteotypic peptides for not yet observed proteins, hence rendering the tool especially useful for plant research.

SUBMITTER: Zimmer D

PROVIDER: S-EPMC6242780 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Artificial Intelligence Understands Peptide Observability and Assists With Absolute Protein Quantification.

Zimmer David D Schneider Kevin K Sommer Frederik F Schroda Michael M Mühlhaus Timo T

Frontiers in plant science 20181113

Targeted mass spectrometry has become the method of choice to gain absolute quantification information of high quality, which is essential for a quantitative understanding of biological systems. However, the design of absolute protein quantification assays remains challenging due to variations in peptide observability and incomplete knowledge about factors influencing peptide detectability. Here, we present a deep learning algorithm for peptide detectability prediction, d::pPop, which allows the ...[more]

PMID: 30483279

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Project description:BackgroundArtificial intelligence (AI)-aided analysis of chest CT expedites the quantification of abnormalities and may facilitate the diagnosis and assessment of the prognosis of subjects with COVID-19.ObjectivesThis study investigates the performance of an AI-aided quantification model in predicting the clinical outcomes of hospitalized subjects with COVID-19 and compares it with radiologists' performance.Subjects and methodsA total of 90 subjects with COVID-19 (men, n = 59 [65.6%]; age, 52.9±16.7 years) were recruited in this cross-sectional study. Quantification of the total and compromised lung parenchyma was performed by two expert radiologists using a volumetric image analysis software and compared against an AI-assisted package consisting of a modified U-Net model for segmenting COVID-19 lesions and an off-the-shelf U-Net model augmented with COVID-19 data for segmenting lung volume. The fraction of compromised lung parenchyma (%CL) was calculated. Based on clinical results, the subjects were divided into two categories: critical (n = 45) and noncritical (n = 45). All admission data were compared between the two groups.ResultsThere was an excellent agreement between the radiologist-obtained and AI-assisted measurements (intraclass correlation coefficient = 0.88, P < 0.001). Both the AI-assisted and radiologist-obtained %CLs were significantly higher in the critical subjects (P = 0.009 and 0.02, respectively) than in the noncritical subjects. In the multivariate logistic regression analysis to distinguish the critical subjects, an AI-assisted %CL ≥35% (odds ratio [OR] = 17.0), oxygen saturation level of <88% (OR = 33.6), immunocompromised condition (OR = 8.1), and other comorbidities (OR = 15.2) independently remained as significant variables in the models. Our proposed model obtained an accuracy of 83.9%, a sensitivity of 79.1%, and a specificity of 88.6% in predicting critical outcomes.ConclusionsAI-assisted measurements are similar to quantitative radiologist-obtained measurements in determining lung involvement in COVID-19 subjects.

Project description:Despite data-independent acquisition (DIA) has been increasingly used for relative protein quantification, DIA-based label-free absolute quantification method has not been fully established. Here we present a novel DIA method using the TPA algorithm (DIA-TPA) for the absolute quantification of protein expressions in human liver microsomal and S9 samples. To validate this method, both data-dependent acquisition (DDA) and DIA experiments were conducted on 36 individual human liver microsome and S9 samples. The MS2-based DIA-TPA was able to quantify approximately twice as many proteins as the MS1-based DDA-TPA method, whereas protein concentrations determined by the two approaches were comparable. To evaluate the accuracy of the DIA-TPA method, we absolutely quantified carboxylesterase 1 concentrations in human liver S9 fractions using an established SILAC internal standard-based proteomic assay; the SILAC results were consistent with those obtained from DIA-TPA analysis. Finally, we employed a unique algorithm in DIA-TPA to distribute the MS signals from shared peptides to individual proteins or isoforms and successfully applied the method to the absolute quantification of several drug-metabolizing enzymes in human liver microsomes. In sum, the DIA-TPA method not only can absolutely quantify entire proteomes and specific proteins, but also has the capability quantifying proteins with shared peptides. SIGNIFICANCE: Data independent acquisition (DIA) has emerged as a powerful approach for relative protein quantification at the whole proteome level. However, DIA-based label-free absolute protein quantification (APQ) method has not been fully established. In the present study, we present a novel DIA-based label-free APQ approach, named DIA-TPA, with the capability absolutely quantifying proteins with shared peptides. The method was validated by comparing the quantification results of DIA-TPA with that obtained from stable isotope-labeled internal standard-based proteomic assays.

Dataset Information

Artificial Intelligence Understands Peptide Observability and Assists With Absolute Protein Quantification.

Publications

Artificial Intelligence Understands Peptide Observability and Assists With Absolute Protein Quantification.

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