scholarly journals CHICKN: extraction of peptide chromatographic elution profiles from large scale mass spectrometry data by means of Wasserstein compressive hierarchical cluster analysis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Olga Permiakova ◽  
Romain Guibert ◽  
Alexandra Kraut ◽  
Thomas Fortin ◽  
Anne-Marie Hesse ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Large Scale ◽  
Clustering Algorithm ◽  
Optimal Transport ◽  
State Of The Art ◽  
Data Representation ◽  
Machine Learning Algorithms ◽  
Mass Spectrometry Data ◽  
Proteomics Data ◽  
Chromatographic Elution

Abstract Background The clustering of data produced by liquid chromatography coupled to mass spectrometry analyses (LC-MS data) has recently gained interest to extract meaningful chemical or biological patterns. However, recent instrumental pipelines deliver data which size, dimensionality and expected number of clusters are too large to be processed by classical machine learning algorithms, so that most of the state-of-the-art relies on single pass linkage-based algorithms. Results We propose a clustering algorithm that solves the powerful but computationally demanding kernel k-means objective function in a scalable way. As a result, it can process LC-MS data in an acceptable time on a multicore machine. To do so, we combine three essential features: a compressive data representation, Nyström approximation and a hierarchical strategy. In addition, we propose new kernels based on optimal transport, which interprets as intuitive similarity measures between chromatographic elution profiles. Conclusions Our method, referred to as CHICKN, is evaluated on proteomics data produced in our lab, as well as on benchmark data coming from the literature. From a computational viewpoint, it is particularly efficient on raw LC-MS data. From a data analysis viewpoint, it provides clusters which differ from those resulting from state-of-the-art methods, while achieving similar performances. This highlights the complementarity of differently principle algorithms to extract the best from complex LC-MS data.

scholarly journals MSpectraAI: a powerful platform for deciphering proteome profiling of multi-tumor mass spectrometry data by using deep neural networks

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Shisheng Wang ◽  
Hongwen Zhu ◽  
Hu Zhou ◽  
Jingqiu Cheng ◽  
Hao Yang
Keyword(s):  
Mass Spectrometry ◽  
Neural Networks ◽  
Large Scale ◽  
Deep Neural Networks ◽  
Spectral Feature ◽  
Mass Spectrometry Data ◽  
Learning Approaches ◽  
Proteomics Data ◽  
Proteome Profiling ◽  
Analytical Technique

Abstract Background Mass spectrometry (MS) has become a promising analytical technique to acquire proteomics information for the characterization of biological samples. Nevertheless, most studies focus on the final proteins identified through a suite of algorithms by using partial MS spectra to compare with the sequence database, while the pattern recognition and classification of raw mass-spectrometric data remain unresolved. Results We developed an open-source and comprehensive platform, named MSpectraAI, for analyzing large-scale MS data through deep neural networks (DNNs); this system involves spectral-feature swath extraction, classification, and visualization. Moreover, this platform allows users to create their own DNN model by using Keras. To evaluate this tool, we collected the publicly available proteomics datasets of six tumor types (a total of 7,997,805 mass spectra) from the ProteomeXchange consortium and classified the samples based on the spectra profiling. The results suggest that MSpectraAI can distinguish different types of samples based on the fingerprint spectrum and achieve better prediction accuracy in MS1 level (average 0.967). Conclusion This study deciphers proteome profiling of raw mass spectrometry data and broadens the promising application of the classification and prediction of proteomics data from multi-tumor samples using deep learning methods. MSpectraAI also shows a better performance compared to the other classical machine learning approaches.

scholarly journals Do we want our data raw? Including binary mass spectrometry data in public proteomics data repositories

PROTEOMICS ◽  
2005 ◽  
Vol 5 (13) ◽  
pp. 3501-3505 ◽  
Author(s):  
Lennart Martens ◽  
Alexey I. Nesvizhskii ◽  
Henning Hermjakob ◽  
Marcin Adamski ◽  
Gilbert S. Omenn ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Mass Spectrometry Data ◽  
Proteomics Data ◽  
Data Repositories

scholarly journals PolySTest: Robust statistical testing of proteomics data with missing values improves detection of biologically relevant features

2019 ◽  
Author(s):  
Veit Schwämmle ◽  
Christina E Hagensen ◽  
Adelina Rogowska-Wrzesinska ◽  
Ole N. Jensen
Keyword(s):  
Mass Spectrometry ◽  
Large Scale ◽  
Missing Values ◽  
Statistical Tests ◽  
Ground Truth ◽  
Statistical Testing ◽  
Molecular Networks ◽  
Proteomics Data ◽  
Biologically Relevant ◽  
Data Browsing

AbstractStatistical testing remains one of the main challenges for high-confidence detection of differentially regulated proteins or peptides in large-scale quantitative proteomics experiments by mass spectrometry. Statistical tests need to be sufficiently robust to deal with experiment intrinsic data structures and variations and often also reduced feature coverage across different biological samples due to ubiquitous missing values. A robust statistical test provides accurate confidence scores of large-scale proteomics results, regardless of instrument platform, experimental protocol and software tools. However, the multitude of different combinations of experimental strategies, mass spectrometry techniques and informatics methods complicate the decision of choosing appropriate statistical approaches. We address this challenge by introducing PolySTest, a user-friendly web service for statistical testing, data browsing and data visualization. We introduce a new method, Miss Test, that simultaneously tests for missingness and feature abundance, thereby complementing common statistical tests by rescuing otherwise discarded data features. We demonstrate that PolySTest with integrated Miss Test achieves higher confidence and higher sensitivity for artificial and experimental proteomics data sets with known ground truth. Application of PolySTest to mass spectrometry based large-scale proteomics data obtained from differentiating muscle cells resulted in the rescue of 10%-20% additional proteins in the identified molecular networks relevant to muscle differentiation. We conclude that PolySTest is a valuable addition to existing tools and instrument enhancements that improve coverage and depth of large-scale proteomics experiments. A fully functional demo version of PolySTest and Miss Test is available via http://computproteomics.bmb.sdu.dk/Apps/PolySTest.

scholarly journals Combining high resolution and exact calibration to boost statistical power: A well-calibrated score function for high-resolution MS2 data

2018 ◽  
Author(s):  
Andy Lin ◽  
J. Jeffry Howbert ◽  
William Stafford Noble
Keyword(s):  
Mass Spectrometry ◽  
High Resolution ◽  
Statistical Power ◽  
State Of The Art ◽  
Score Function ◽  
Shotgun Proteomics ◽  
Database Search ◽  
Mass Spectrometry Data ◽  
P Value ◽  
Score Functions

AbstractTo achieve accurate assignment of peptide sequences to observed fragmentation spectra, a shotgun proteomics database search tool must make good use of the very high resolution information produced by state-of-the-art mass spectrometers. However, making use of this information while also ensuring that the search engine’s scores are well calibrated—i.e., that the score assigned to one spectrum can be meaningfully compared to the score assigned to a different spectrum—has proven to be challenging. Here, we describe a database search score function, the “residue evidence” (res-ev) score, that achieves both of these goals simultaneously. We also demonstrate how to combine calibrated res-ev scores with calibrated XCorr scores to produce a “combined p-value” score function. We provide a benchmark consisting of four mass spectrometry data sets, which we use to compare the combined p-value to the score functions used by several existing search engines. Our results suggest that the combined p-value achieves state-of-the-art performance, generally outperforming MS Amanda and Morpheus and performing comparably to MS-GF+. The res-ev and combined p-value score functions are freely available as part of the Tide search engine in the Crux mass spectrometry toolkit (http://crux.ms).

scholarly journals Efficient exploratory clustering analyses in large-scale exploration processes

2021 ◽  
Author(s):  
Manuel Fritz ◽  
Michael Behringer ◽  
Dennis Tschechlov ◽  
Holger Schwarz
Keyword(s):  
Large Scale ◽  
Clustering Algorithm ◽  
Comprehensive Evaluation ◽  
State Of The Art ◽  
Clustering Algorithms ◽  
Search Space ◽  
Large Datasets ◽  
Search Spaces ◽  
Multiple Challenges ◽  
The One

AbstractClustering is a fundamental primitive in manifold applications. In order to achieve valuable results in exploratory clustering analyses, parameters of the clustering algorithm have to be set appropriately, which is a tremendous pitfall. We observe multiple challenges for large-scale exploration processes. On the one hand, they require specific methods to efficiently explore large parameter search spaces. On the other hand, they often exhibit large runtimes, in particular when large datasets are analyzed using clustering algorithms with super-polynomial runtimes, which repeatedly need to be executed within exploratory clustering analyses. We address these challenges as follows: First, we present LOG-Means and show that it provides estimates for the number of clusters in sublinear time regarding the defined search space, i.e., provably requiring less executions of a clustering algorithm than existing methods. Second, we demonstrate how to exploit fundamental characteristics of exploratory clustering analyses in order to significantly accelerate the (repetitive) execution of clustering algorithms on large datasets. Third, we show how these challenges can be tackled at the same time. To the best of our knowledge, this is the first work which simultaneously addresses the above-mentioned challenges. In our comprehensive evaluation, we unveil that our proposed methods significantly outperform state-of-the-art methods, thus especially supporting novice analysts for exploratory clustering analyses in large-scale exploration processes.

scholarly journals A semi-supervised Bayesian approach for simultaneous protein sub-cellular localisation assignment and novelty detection

2020 ◽  
Author(s):  
Oliver M. Crook ◽  
Aikaterini Geladaki ◽  
Daniel J.H. Nightingale ◽  
Owen Vennard ◽  
Kathryn S. Lilley ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Bayesian Approach ◽  
Novelty Detection ◽  
Machine Learning Algorithms ◽  
Proteomics Data ◽  
Diverse Range ◽  
Biologically Relevant ◽  
Cellular Localisation ◽  
Associated Proteins ◽  
Experimental Protocols

AbstractThe cell is compartmentalised into complex micro-environments allowing an array of specialised biological processes to be carried out in synchrony. Determining a protein’s sub-cellular localisation to one or more of these compartments can therefore be a first step in determining its function. High-throughput and high-accuracy mass spectrometry-based sub-cellular proteomic methods can now shed light on the localisation of thousands of proteins at once. Machine learning algorithms are then typically employed to make protein-organelle assignments. However, these algorithms are limited by insufficient and incomplete annotation. We propose a semi-supervised Bayesian approach to novelty detection, allowing the discovery of additional, previously unannotated sub-cellular niches. Inference in our model is performed in a Bayesian framework, allowing us to quantify uncertainty in the allocation of proteins to new sub-cellular niches, as well as in the number of newly discovered compartments. We apply our approach across 10 mass spectrometry based spatial proteomic datasets, representing a diverse range of experimental protocols. Application of our approach to hyper LOPIT datasets validates its utility by recovering enrichment with chromatin-associated proteins without annotation and uncovers sub-nuclear compartmentalisation which was not identified in the original analysis. Moreover, using sub-cellular proteomics data from Saccharomyces cerevisiae, we uncover a novel group of proteins trafficking from the ER to the early Golgi apparatus. Overall, we demonstrate the potential for novelty detection to yield biologically relevant niches that are missed by current approaches.

scholarly journals MEMO: Mass Spectrometry-based Sample Vectorization to Explore Chemodiverse Datasets

2021 ◽  
Author(s):  
Arnaud Gaudry ◽  
Florian Huber ◽  
Louis-Felix Nothias ◽  
Sylvian Cretton ◽  
Marcel Kaiser ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Large Scale ◽  
State Of The Art ◽  
Mass Spectrometric ◽  
Bioactive Molecules ◽  
Computational Time ◽  
Mass Spectral ◽  
Experimental Variation ◽  
Alignment Step ◽  
Feature Alignment

In natural products research, chemodiverse extracts coming from multiple organisms are explored for novel bioactive molecules, sometimes over extended periods. Samples are usually analyzed by liquid chromatography coupled with fragmentation mass spectrometry to acquire informative mass spectral ensembles. Such data is then exploited to establish relationships among analytes or samples (e.g. via molecular networking) and annotate metabolites. However, the comparison of samples profiled in different batches is challenging with current metabolomics methods. Indeed, the experimental variation - changes in chromatographical or mass spectrometric conditions - often hinders the direct comparison of the profiled samples. Here we introduce MEMO - MS2 BasEd SaMple VectOrization - a method allowing to cluster large amounts of chemodiverse samples based on their LC-MS/MS profiles in a retention time agnostic manner. This method is particularly suited for heterogeneous and chemodiverse sample sets. MEMO demonstrated similar clustering performance as state-of-the-art metrics taking into account fragmentation spectra. More importantly, such performance was achieved without the requirement of a prior feature alignment step and in a significantly shorter computational time. MEMO thus allows the comparison of vast ensembles of samples, even when analyzed over long periods of time, and on different chromatographic or mass spectrometry platforms. This new addition to the computational metabolomics toolbox should drastically expand the scope of large-scale comparative analysis.

scholarly journals PolySTest: Robust Statistical Testing of Proteomics Data with Missing Values Improves Detection of Biologically Relevant Features

2020 ◽  
Vol 19 (8) ◽  
pp. 1396-1408 ◽  
Author(s):  
Veit Schwämmle ◽  
Christina E. Hagensen ◽  
Adelina Rogowska-Wrzesinska ◽  
Ole N. Jensen
Keyword(s):  
Mass Spectrometry ◽  
Large Scale ◽  
Missing Values ◽  
Statistical Tests ◽  
Ground Truth ◽  
Statistical Testing ◽  
Molecular Networks ◽  
Proteomics Data ◽  
Biologically Relevant ◽  
Data Browsing

Statistical testing remains one of the main challenges for high-confidence detection of differentially regulated proteins or peptides in large-scale quantitative proteomics experiments by mass spectrometry. Statistical tests need to be sufficiently robust to deal with experiment intrinsic data structures and variations and often also reduced feature coverage across different biological samples due to ubiquitous missing values. A robust statistical test provides accurate confidence scores of large-scale proteomics results, regardless of instrument platform, experimental protocol and software tools. However, the multitude of different combinations of experimental strategies, mass spectrometry techniques and informatics methods complicate the decision of choosing appropriate statistical approaches. We address this challenge by introducing PolySTest, a user-friendly web service for statistical testing, data browsing and data visualization. We introduce a new method, Miss test, that simultaneously tests for missingness and feature abundance, thereby complementing common statistical tests by rescuing otherwise discarded data features. We demonstrate that PolySTest with integrated Miss test achieves higher confidence and higher sensitivity for artificial and experimental proteomics data sets with known ground truth. Application of PolySTest to mass spectrometry based large-scale proteomics data obtained from differentiating muscle cells resulted in the rescue of 10–20% additional proteins in the identified molecular networks relevant to muscle differentiation. We conclude that PolySTest is a valuable addition to existing tools and instrument enhancements that improve coverage and depth of large-scale proteomics experiments. A fully functional demo version of PolySTest and Miss test is available via http://computproteomics.bmb.sdu.dk/Apps/PolySTest.

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