Scanning electron micrograph of Mycobacterium tuberculosis, the pathogen that causes TB (CDC).
Scanning electron micrograph of Mycobacterium tuberculosis, the pathogen that causes TB (CDC).

Biography

My research interests lie primarily in the modeling of infectious diseases, both on the molecular level (using approaches from computational and systems biology) as well as on the population level (using approaches from epidemiology and biostatistics). I am particularlly interested in the interactions between science, medicine and policy as they relate to improving patient outcomes, especially in low-income, low-resource settings.

I hold a PhD in Applied Mathematics from MIT and a BSc in Mathematics and Computer Science from McGill University. My doctoral work focused on metabolic models of tuberculosis (TB). I have been working in Ted Cohen's group since September 2012. I recently submitted a paper on a joint model of the TB and HIV epidemics in Southern Africa and I am currently working on identifying mixed TB infection in a population.

Between my PhD and my postdoctoral fellowship I worked as a computational biologist at Pfizer, developing methods for interpreting gene expression, genetic and metabolomic data using a large network of known biological relationships. I also spent some time working at the Massachusetts General Hospital and the Clinton Health Access Initiative.

I am actively looking for excellent, highly motivated graduate students and postdoctoral fellows (see the ad on MathJobs). If you are interested in working on any of these topics please send me an email!

News In February 2016 I was selected as an Alfred P. Sloan Research Fellow in Computational and Evolutionary Molecular Biology. See the announcement on the Simon Fraser University website.

Research

As an applied mathematician I use a variety of mathematical methods to address one of today's most pressing problems: infectious disease epidemics. I am pursuing a cross-disciplinary approach to the study of infectious disease that incorporates computational biology, phylogenetics, epidemiology, and economic game theory.

Computational biology: analyzing metabolic networks, with applications to M. tuberculosis.

My doctoral research involved the modeling of the metabolism of TB. I developed an algorithmic pipeline called MetaMerge which allowed me to reconcile differences in format, nomenclature, and annotation between two models of TB metabolism. MONGOOSE, another doctoral project of mine, is a tool for analyzing metabolic network models in exact arithmetic, resulting in consistent, reproducible predictions.

Epidemiology: compartmental modeling of the tuberculosis-HIV/AIDS co-epidemic.

As part of my postdoctoral research I developed a compartmental model that accounts for the joint natural history of TB and HIV. I calibrated this model to data available for South Africa and used it to investigate the effects of various interventions aimed at reducing the burden of these diseases in order to help policy-makers select the most impactful and cost-effective one among many alternatives.

Phylogenetics: analyzing prevalence and transmission patterns of mixed tuberculosis infection.

I am developing a method for elucidating the genetic forces at play in the TB epidemics in South Africa and South America by using the TB strains' MIRU-VNTR fingerprints. My method integrates uncertainties about the strain composition of a sample and the phylogenetic relationship between the strains into a robust algorithmic framework to identify patients with mixed infections or mutating strains.

Economic game theory: modeling the alignment of incentives between public and private sector.

I am currently pursuing a collaboration examining the economic incentive structures for the interaction between public and private medical sectors in India. Using a principal-agent paradigm and incorporating the stochasticity of the health outcomes allows us to combine a population-level stochastic model of the course of an infectious disease epidemic with a game-theoretic model of dynamic contract negotiation.

Publications

2016

Within-Host Heterogeneity of Mycobacterium tuberculosis Infection Is Associated With Poor Early Treatment Response: A Prospective Cohort Study (HTML)

Ted Cohen, Leonid Chindelevitch, Reshma Misra, Maria Kempner, Jerome Galea et al.

Journal of Infectious Diseases, 213 (11): 1796-1799  (2016)

ClassTR: classifying within-host heterogeneity based on tandem repeats with application to Mycobacterium tuberculosis infections. (HTML)

Leonid Chindelevitch, Caroline Colijn, Prashini Moodley, Douglas Wilson, Ted Cohen.

PLoS Computational Biology, 12(2):e1004475  (2016)

2015

"Do genome-scale models need exact solvers or clearer standards?" (HTML)

Leonid Chindelevitch, Jason Trigg, Aviv Regev, Bonnie Berger.

Molecular Systems Biology, 11(10):830 (2015)

Evaluating the potential impact of enhancing HIV treatment and tuberculosis control programmes on the burden of tuberculosis (HTML)

Leonid Chindelevitch, Nicolas Menzies, Carel Pretorius, John Stover, Joshua Salomon, Ted Cohen.

Journal of the Royal Society Interface, 12:106 (2015)

2014

An exact arithmetic toolbox for a consistent and reproducible structural analysis of metabolic network models (HTML)

Leonid Chindelevitch, Jason Trigg, Aviv Regev, Bonnie Berger.

Nature Communications, 5:4893 (2014)

Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models (HTML)

Jeffrey Eaton, Nicolas Menzies, John Stover, Valentina Cambiano, Leonid Chindelevitch et al.

The Lancet Global Health, Volume 2, Issue 1, January 2014, Pages e23-e34

The potential effects of changing HIV treatment policy on TB outcomes in South Africa: results from three TB-HIV transmission models (HTML)

Carel Pretorius, Nick Menzies, Leonid Chindelevitch, Ted Cohen, Anne Cori et al.

AIDS (2014) January Supplement (1) S25-34

2013

Optimizing a global alignment of protein interaction networks (HTML)

Chindelevitch, Leonid; Ma, Cheng-Yu; Liao, Chung-Shou; Berger, Bonnie.

Bioinformatics, Volume 29, Issue 21, 2013, Pages 2765-2773

2012

Causal reasoning on biological networks: interpreting transcriptional changes (HTML)

Chindelevitch, Leonid; Ziemek, Daniel; Enayetallah, Ahmed; Randhawa, Ranjit; Sidders, Ben; Brockel, Christoph; Huang, Enoch S.

Bioinformatics, Volume 28, Issue 8, 2012, Pages 1114-1121

MetaMerge: scaling up genome-scale metabolic reconstructions with application to Mycobacterium tuberculosis (PDF)

Chindelevitch, Leonid; Stanley, Sarah; Hung, Deborah; Regev, Aviv; Berger, Bonnie.

Genome Biology, Volume 3, Issue 1, 2012, Page R6

Assessing statistical significance in causal graphs (HTML)

Chindelevitch, Leonid; Loh, Po-Ru; Enayetallah, Ahmed; Berger, Bonnie; Ziemek, Daniel.

BMC Bioinformatics, Volume 3, Issue 1, 2012, Page 35

Correlation set analysis: detecting active regulators in disease populations using prior causal knowledge (HTML)

Huang, Chia-Ling; Lamb, John; Chindelevitch, Leonid; Kostrowicki, Jarek; Guinney, Justin; DeLisi, Charles; Ziemek, Daniel.

BMC Bioinformatics, Volume 3, Issue 1, 2012, Page 46

2011

Causal reasoning on biological networks: Interpreting transcriptional changes (PDF)

Chindelevitch, Leonid; Ziemek, Daniel; Enayetallah, Ahmed; Randhawa, Ranjit; Sidders, Ben; Brockel, Christoph; Huang, Enoch.

Research in Computational Molecular Biology, 2011, Pages 34-37

Metabolic network analysis demystified (PDF)

Chindelevitch, Leonid; Regev, Aviv; Berger, Bonnie.

Research in Computational Molecular Biology, 2011, Pages 31-33

2010

Local optimization for global alignment of protein interaction networks (PDF)

Chindelevitch, Leonid; Liao, Chung-Shou; Berger, Bonnie.

Pacific Symposium on Biocomputing, Volume 15, 2010, Pages 123-132

2008

Inverting the Viterbi algorithm: an abstract framework for structure design (PDF)

Schnall-Levin, Michael; Chindelevitch, Leonid; Berger, Bonnie.

Proceedings of the 25th International Conference on Machine Learning, 2008, Pages 904-911

2007

Error analysis and preconditioning for an enhanced DtN-FE algorithm for exterior scattering problems (HTML)

Chindelevitch, Leonid; Nicholls, David P; Nigam, Nilima.

Journal of Computational and Applied Mathematics, Volume 2004, Issue 2, 2007, Pages 493-504

2006

On the inference of parsimonious indel evolutionary scenarios (HTML)

Chindelevitch, Leonid; Li, Zhentao; Blais, Eric; Blanchette, Mathieu.

Journal of Bioinformatics And Computational Biology, Volume 4, Issue 3, 2006, Pages 721-744

Programs

MetaMerge: combining and reconciling metabolic network model reconstructions

MetaMerge is a package for combining different metabolic network models of the same organism by reconciling the differences in annotation, coverage and model specification. We successfully used it to combine two existing metabolic models of TB. MetaMerge is available for download at genomebiology.com.

MONGOOSE: exact arithmetic-based analysis of metabolic network models

MONGOOSE (MetabOlic Network GrOwth Optimization Solved Exactly) is a package for structural analysis and refinement of constraint-based metabolic networks. Unlike other existing software, MONGOOSE uses exact rational arithmetic, which makes its results certifiably accurate. MONGOOSE is available for download at mongoose.csail.mit.edu.

ClassTR: classifying complex TB infections

ClassTR is a program that takes microsatellite (molecular fingerprinting) data of a collection of TB strains and for each strain containing loci with more than one variant, determines whether it's more likely to be the result of microevolution within the host or multiple infections. ClassTR is available for download as an R package at PLoS Computational Biology.

Lab Members

Our lab is a friendly, dynamic group of people, ranging from first-year undergraduates to senior postdocs. We have biweekly meetings and regular social events. Please email me if you are interested in joining our lab!

  • Fang Zhang

    PhD student

    Modelling tuberculosis resistance acquisition and transmission in a hugh-burden setting

  • Maryam Hayati

    PhD student

    Inferring transmission trees from phylogenetic trees

  • Ali Pazoki

    MSc student

    Assessing strain diversity in Borrelia

  • Nicole Althermeler

    Visiting PhD student

    1. Inferring ancestral Beijing strains

    2. Finding genome rearrangements in Mycobacterium tuberculosis

  • Jack Seary

    Summer student

    Determining timestamps for the expressions levels of genes involved in circadian rhythm

  • Emre Erhan

    Summer student

    Ancestral reconstruction of Shanghai tuberculosis strain phylogeny from copy numbers

  • Rita Vityaz

    Summer student

    1. Finding MIRU-VNTR copy numbers

    2. Finding genome rearrangements in Mycobacterium tuberculosis

  • Abby Leung

    Summer student

    Determining timestamps for the expressions levels of genes involved in circadian rhythm

  • Nithum Thain

    Postdoctoral Fellow, Alum

    Machine learning approaches for classifying tuberculosis lineages from MIRU-VNTR data

    Now: Google Research Fellow

  • Nathan Nastili

    Summer student

    Identification of pediatric vasculitis signatures using machine learning

    Now: Graduate Student, Cornell University

Contact

TASC 1 9425
8888 University Drive,
Burnaby, BC, V5A 1S6

+1 (778) 782-4973

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