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Accurate Profiling of Microbial Communities from Massively Parallel Sequencing Using Convex Optimization

  • Or Zuk
  • Amnon Amir
  • Amit Zeisel
  • Ohad Shamir
  • Noam Shental
Part of the Lecture Notes in Computer Science book series (LNCS, volume 8214)

Abstract

We describe the Microbial Community Reconstruction (MCR) Problem, which is fundamental for microbiome analysis. In this problem, the goal is to reconstruct the identity and frequency of species comprising a microbial community, using short sequence reads from Massively Parallel Sequencing (MPS) data obtained for specified genomic regions. We formulate the problem mathematically as a convex optimization problem and provide sufficient conditions for identifiability, namely the ability to reconstruct species identity and frequency correctly when the data size (number of reads) grows to infinity. We discuss different metrics for assessing the quality of the reconstructed solution, including a novel phylogenetically-aware metric based on the Mahalanobis distance, and give upper-bounds on the reconstruction error for a finite number of reads under different metrics. We propose a scalable divide-and-conquer algorithm for the problem using convex optimization, which enables us to handle large problems (with \(\sim\!10^6\) species). We show using numerical simulations that for realistic scenarios, where the microbial communities are sparse, our algorithm gives solutions with high accuracy, both in terms of obtaining accurate frequency, and in terms of species phylogenetic resolution.

Keywords

Microbial Community Reconstruction Massively Parallel Sequencing Short Reads Convex Optimization 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Or Zuk
    • 1
    • 2
  • Amnon Amir
    • 3
  • Amit Zeisel
    • 3
  • Ohad Shamir
    • 4
  • Noam Shental
    • 5
  1. 1.Broad Institute of MIT and HarvardUSA
  2. 2.Toyota Technological Institute at ChicagoUSA
  3. 3.Department of Physics of Complex SystemsWeizmann Institute of ScienceIsrael
  4. 4.Microsoft ResearchUK
  5. 5.Department of Computer ScienceThe Open University of IsraelIsrael

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