Liquid chromatography mass spectrometry-based proteomics: Biological and technological aspects

TL;DR

This paper reviews the biological and technological aspects of mass spectrometry-based proteomics, highlighting key statistical challenges in protein identification and quantification within the bottom-up approach.

Contribution

It provides an overview of bottom-up proteomics and discusses the main statistical issues involved in protein identification and quantification.

Findings

Identification of proteins in complex samples

Quantification of protein abundance levels

Discussion of statistical methods for proteomics analysis

Abstract

Mass spectrometry-based proteomics has become the tool of choice for identifying and quantifying the proteome of an organism. Though recent years have seen a tremendous improvement in instrument performance and the computational tools used, significant challenges remain, and there are many opportunities for statisticians to make important contributions. In the most widely used "bottom-up" approach to proteomics, complex mixtures of proteins are first subjected to enzymatic cleavage, the resulting peptide products are separated based on chemical or physical properties and analyzed using a mass spectrometer. The two fundamental challenges in the analysis of bottom-up MS-based proteomics are as follows: (1) Identifying the proteins that are present in a sample, and (2) Quantifying the abundance levels of the identified proteins. Both of these challenges require knowledge of the biological and technological context that gives rise to observed data, as well as the application of sound statistical principles for estimation and inference. We present an overview of bottom-up proteomics and outline the key statistical issues that arise in protein identification and quantification.