Metamorphosis: the Coming Transformation of Translational Systems Biology

One morning, as Gregorina Samsa was waking up from anxious dreams, she discovered that she had become afflicted with certain mysterious flu-like symptoms that appeared without any warning. Equally irritating, this capricious metamorphosis seemed impervious to a rational explanation in terms of causes and effects. "What’s happened to me?" she thought. Before seeing a doctor, she decided to find out more about what might ail her. She logged on to a Web site where she annotated a timeline with what she could remember. Since March, she’d had more headaches than usual, and then in April she had begun to experience more fatigue after exercise, and as of July she had also experienced occasional lapses in memory. "Why don’t I go back to sleep for a little while longer and forget all this foolishness," she thought. As she was about to abandon this errand, the system came back to life with a barrage of questions: Is she female? Had she experienced any significant stress in the past few months? Had she noticed any joint or muscle pain? It also obtained her permission to download her genomic profile.

[1]  B. Efron.  Large-Scale Simultaneous Hypothesis Testing , 2004 .

[2]  Korbinian Strimmer,et al.  From correlation to causation networks: a simple approximate learning algorithm and its application to high-dimensional plant gene expression data , 2007, BMC Systems Biology.

[3]  John D. Storey,et al.  Statistical significance for genomewide studies , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Wesley C. Salmon,et al.  Causality: Production and Propagation , 1980, PSA: Proceedings of the Biennial Meeting of the Philosophy of Science Association.

[5]  Michal Linial,et al.  Using Bayesian Networks to Analyze Expression Data , 2000, J. Comput. Biol..

[6]  R. Tibshirani,et al.  Empirical bayes methods and false discovery rates for microarrays , 2002, Genetic epidemiology.

[7]  Franz von Kutschera,et al.  Causation , 1993, J. Philos. Log..

[8]  Simon Kasif,et al.  Systems Biology via Redescription and Ontologies (III): Protein Classification Using Malaria Parasite's Temporal Transcriptomic Profiles , 2008, 2008 IEEE International Conference on Bioinformatics and Biomedicine.

[9]  P. Suppes.  A Probabilistic Theory Of Causality , 1970 .

[10]  Christopher J. Langmead,et al.  Towards Inference and Learning in Dynamic Bayesian Networks using Generalized Evidence , 2008 .

[11]  J. Derisi,et al.  The Transcriptome of the Intraerythrocytic Developmental Cycle of Plasmodium falciparum , 2003, PLoS biology.

[12]  Hiroaki Kitano,et al.  Biological robustness , 2008, Nature Reviews Genetics.

[13]  Stephan Merz,et al.  Model Checking , 2000 .

[14]  Richard Scheines,et al.  Constructing Bayesian Network Models of Gene Expression Networks from Microarray Data , 2000 .

[15]  Bud Mishra,et al.  Systems biology via redescription and ontologies (I): finding phase changes with applications to malaria temporal data , 2007, Systems and Synthetic Biology.

[16]  Kevin P. Murphy,et al.  Learning the Structure of Dynamic Probabilistic Networks , 1998, UAI.

[17]  Tom Burr,et al.  Causation, Prediction, and Search , 2003, Technometrics.

[18]  J. Pearl.  Causality: Models, Reasoning and Inference , 2000 .

[19]  Bengt Jonsson,et al.  A logic for reasoning about time and reliability , 1990, Formal Aspects of Computing.

[20]  T. Cai,et al.  Estimating the Null and the Proportion of Nonnull Effects in Large-Scale Multiple Comparisons , 2006, math/0611108.

[21]  S. Dudoit,et al.  Multiple Hypothesis Testing in Microarray Experiments , 2003 .

[22]  M. Newton.  Large-Scale Simultaneous Hypothesis Testing: The Choice of a Null Hypothesis , 2008 .

[23]  Y. Benjamini,et al.  THE CONTROL OF THE FALSE DISCOVERY RATE IN MULTIPLE TESTING UNDER DEPENDENCY , 2001 .

[24]  David Heckerman,et al.  A Bayesian Approach to Learning Causal Networks , 1995, UAI.