Dataset Information

Mass spectrometry based metabolomics for in vitro systems pharmacology: pitfalls, challenges, and computational solutions.

ABSTRACT:

Introduction

Mass spectrometry based metabolomics has become a promising complement and alternative to transcriptomics and proteomics in many fields including in vitro systems pharmacology. Despite several merits, metabolomics based on liquid chromatography mass spectrometry (LC-MS) is a developing area that is yet attached to several pitfalls and challenges. To reach a level of high reliability and robustness, these issues need to be tackled by implementation of refined experimental and computational protocols.

Objectives

This study illustrates some key pitfalls in LC-MS based metabolomics and introduces an automated computational procedure to compensate for them.

Method

Non-cancerous mammary gland derived cells were exposed to 27 chemicals from four pharmacological classes plus a set of six pesticides. Changes in the metabolome of cell lysates were assessed after 24 h using LC-MS. A data processing pipeline was established and evaluated to handle issues including contaminants, carry over effects, intensity decay and inherent methodology variability and biases. A key component in this pipeline is a latent variable method called OOS-DA (optimal orthonormal system for discriminant analysis), being theoretically more easily motivated than PLS-DA in this context, as it is rooted in pattern classification rather than regression modeling.

Result

The pipeline is shown to reduce experimental variability/biases and is used to confirm that LC-MS spectra hold drug class specific information.

Conclusion

LC-MS based metabolomics is a promising methodology, but comes with pitfalls and challenges. Key difficulties can be largely overcome by means of a computational procedure of the kind introduced and demonstrated here. The pipeline is freely available on www.github.com/stephanieherman/MS-data-processing.

SUBMITTER: Herman S

PROVIDER: S-EPMC5438430 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Mass spectrometry based metabolomics for in vitro systems pharmacology: pitfalls, challenges, and computational solutions.

Herman Stephanie S Emami Khoonsari Payam P Aftab Obaid O Krishnan Shibu S Strömbom Emil E Larsson Rolf R Hammerling Ulf U Spjuth Ola O Kultima Kim K Gustafsson Mats M

Metabolomics : Official journal of the Metabolomic Society 20170519 7

<h4>Introduction</h4>Mass spectrometry based metabolomics has become a promising complement and alternative to transcriptomics and proteomics in many fields including in vitro systems pharmacology. Despite several merits, metabolomics based on liquid chromatography mass spectrometry (LC-MS) is a developing area that is yet attached to several pitfalls and challenges. To reach a level of high reliability and robustness, these issues need to be tackled by implementation of refined experimental and ...[more]

PMID: 28596718

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Dataset Information

Mass spectrometry based metabolomics for in vitro systems pharmacology: pitfalls, challenges, and computational solutions.

Introduction

Objectives

Method

Result

Conclusion

Publications

Mass spectrometry based metabolomics for in vitro systems pharmacology: pitfalls, challenges, and computational solutions.

Similar Datasets

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