title: MetTailor: dynamic block summary and intensity normalization for robust analysis of mass spectrometry data in metabolomics.
abstract: BACKGROUND
  Accurate cross-sample peak alignment and reliable intensity normalization is a critical step for robust quantitative analysis in untargetted metabolomics since tandem mass spectrometry (MS/MS) is rarely used for compound identification. Therefore shortcomings in the data processing steps can easily introduce false positives due to misalignments and erroneous normalization adjustments in large sample studies.
  
  
  RESULTS
  In this work, we developed a software package MetTailor featuring two novel data preprocessing steps to remedy drawbacks in the existing processing tools. First, we propose a novel dynamic block summarization (DBS) method for correcting misalignments from peak alignment algorithms, which alleviates missing data problem due to misalignments. For the purpose of verifying correct re-alignments, we propose to use the cross-sample consistency in isotopic intensity ratios as a quality metric. Second, we developed a flexible intensity normalization procedure that adjusts normalizing factors against the temporal variations in total ion chromatogram (TIC) along the chromatographic retention time (RT). We first evaluated the DBS algorithm using a curated metabolomics dataset, illustrating that the algorithm identifies misaligned peaks and correctly realigns them with good sensitivity. We next demonstrated the DBS algorithm and the RT-based normalization procedure in a large-scale dataset featuring >100 sera samples in primary Dengue infection study. Although the initial alignment was successful for the majority of peaks, the DBS algorithm still corrected ∼7000 misaligned peaks in this data and many recovered peaks showed consistent isotopic patterns with the peaks they were realigned to. In addition, the RT-based normalization algorithm efficiently removed visible local variations in TIC along the RT, without sacrificing the sensitivity of detecting differentially expressed metabolites.
  
  
  METHODS
  The R package MetTailor is freely available at the SourceForge website http://mettailor.sourceforge.net/.
  
  
  BACKGROUND
  hyung_won_choi@nuhs.edu.sg
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
authors.forename: Gengbo
authors.initials: G
authors.lastname: Chen
authors.affiliation: Interdisciplinary Research Group in Infectious Diseases, Singapore-MIT Alliance for Research & Technology, Singapore, Singapore and.
authors.forename: Liang
authors.initials: L
authors.lastname: Cui
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
authors.forename: Guo Shou
authors.initials: GS
authors.lastname: Teo
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore, National University of Singapore Environment Research Institute, Singapore, Singapore.
authors.forename: Choon Nam
authors.initials: CN
authors.lastname: Ong
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
authors.forename: Chuen Seng
authors.initials: CS
authors.lastname: Tan
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
authors.forename: Hyungwon
authors.initials: H
authors.lastname: Choi
mesh_terms: D000465:Algorithms; D002138:Calibration; D002845:Chromatography; D019992:Databases as Topic; D013058:Mass Spectrometry / Q000379:methods*; D055432:Metabolomics / Q000379:methods*; D012984:Software