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Ecological Modeling from Time-Series Inference: Insight into Dynamics and Stability of Intestinal Microbiota (2013)
PRESENTED BY: GUY SHAPIRA
BY:RICHARD R. STEIN 1 * . , VANNI BUCCI 1 * . , NORA C. TOUSSAINT 2 , CHARLIE G. BUFFIE 2 , GUNNAR RÄTSCH 1 , ERIC G. PAMER 2 , CHRIS SANDER 1 , JOÃO B. XAVIER 1 * COMPUTATIONAL BIOLOGY PROGRAM, SLOAN -KETTERING INSTITUTE, MEMORI AL SLOAN-KETTERING CANCER CENTER, NEW YORK, NEW YORK, UNITED STATES OF AMERICA, 2 IMMUNOLOGY PROGRAM, SLOAN -KETTERING INSTITUTE, MEMORIAL SLOAN -KETTERING CAN CER CENTER, NEW YORK, NEW YORK, UNITED STATES OF AMERICA
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Outline
• Microbial effects on human health
• Previously shown methods and their shortcomings
• Overview of new method
• Results
• Discussion
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Intestinal microbiome: Friend or foe
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The methods discussed thus far
• Exclusively correlative (non-directional) inference of interaction
• No predictive power • Limited to a single time-frame
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Static analyses
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Microbes are alive
The microbiome is highly dynamic, effected by various factors:
• Diet
• Competition
• Drugs
• Infections
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Lotka-Volterra Predator-prey model (1910)
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Modelling an ecological community
𝑑
𝑑𝑡𝑥𝑖 𝑡 = 𝜇𝑖𝑥𝑖 𝑡 + 𝑥𝑖 𝑡 𝑀𝑖𝑗𝑥𝑗 𝑡
𝐿
𝑗=1
+ 𝑥𝑖 𝑡 𝜀𝑖𝑙𝜐𝑙 𝑡
𝑃
𝑙=1
𝑖 = 1,… , 𝐿 Species of interest
𝑥𝑖 𝑡 Concentration of i at time point t
𝜇𝑖 Growth rate of i
𝑀𝑖𝑗 Effect of j on i during interaction
𝜀𝑖𝑙 Susceptibility of i to perturbation l
𝜐𝑙 𝑡 Susceptibility of i to perturbation l
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𝛥𝑙𝑛
Converting continuous to discrete
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𝑚𝑖𝑛 𝑀𝜇𝐸 𝑌 − 𝐹 +𝜆𝑀22 𝑀 +𝜆𝜇2
2 𝜇 +𝜆𝐸22 𝐸
22
Estimating parameters with regularized regression
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K-Fold cross validation
Shown with k=5, authors used k=3
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Mouse experiment
3 mice groups: • Administration of Clostridium difficile, a bacterial pathogen. • Administration of Clindamycin, an antibiotic. • Administration of Clindamycin, followed by an administration of C. difficile the day after.
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Effects of Clostridium difficile
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Effects of Clindamycin
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Effects of Clindamycin + Clostridium difficile
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Predictive power
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The interplay between microbial taxa
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The microbial drama unfolds
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The microbial drama unfolds
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The microbial drama unfolds
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The microbial drama unfolds
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Current shortcomings and possibilities for improvement
• Currently tested with absolute data only (antibiotically treated to extinction). • Only supports with pairwise, second order interactions. • Currently only works with roughly estimated and transformed count data
• Works in a rough genus-level resolution and includes only the most common of those
• More specific and gradual experimental data for empirical modeling of specific effects
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Discussion
• What is the best possible way to improve the current method (whether it’s a model improvement, addition, data consideration)?
• Are you more averse to antibiotic treatment after seeing the results of the experiment