Abstract
Deciphering the developmental program of an embryo is a fundamental question in biology. Landmark papers [9,10] have recently shown how computational models of gene regulatory networks provide system-level causal understanding of the developmental processes of the sea urchin, and enable powerful predictive capabilities. A crucial aspect of the work is empirically deriving plausible models that explain all the known experimental data, a task that becomes infeasible in practice due to the inherent complexity of the biological systems. We present a generic Satisfiability Modulo Theories based approach to analyze and synthesize data constrained models. We apply our approach to the sea urchin embryo, and successfully improve the state-of-the-art by synthesizing, for the first time, models that explain all the experimental observations in [10]. A strength of the proposed approach is the combination of accurate synthesis procedures for deriving biologically plausible models with the ability to prove inconsistency results, showing that for a given set of experiments and possible class of models no solution exists, and thus enabling practical refutation of biological models.
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Bartocci, E., Bortolussi, L., Nenzi, L.: A temporal logic approach to modular design of synthetic biological circuits. In: Gupta, A., Henzinger, T.A. (eds.) CMSB 2013. LNCS (LNBI), vol. 8130, pp. 164–177. Springer, Heidelberg (2013)
Batt, G., Yordanov, B., Weiss, R., Belta, C.: Robustness analysis and tuning of synthetic gene networks. Bioinformatics 23(18) (2007)
Chaudhuri, S., Clochard, M., Solar-Lezama, A.: Bridging Boolean and quantitative synthesis using smoothed proof search. In: POPL. ACM (2014)
de Moura, L., Bjørner, N.: Z3: An efficient SMT solver. In: Ramakrishnan, C.R., Rehof, J. (eds.) TACAS 2008. LNCS, vol. 4963, pp. 337–340. Springer, Heidelberg (2008)
Koksal, A., Pu, Y., Srivastava, S., Bodik, R., Fisher, J., Piterman, N.: Synthesis of biological models from mutation experimentss. In: SIGPLAN-SIGACT Symposium on Principles of Programming Languages. ACM (2013)
Kugler, H., Plock, C., Roberts, A.: Synthesizing Biological Theories. In: Gopalakrishnan, G., Qadeer, S. (eds.) CAV 2011. LNCS, vol. 6806, pp. 579–584. Springer, Heidelberg (2011)
Kugler, H., Pnueli, A., Stern, M.J., Hubbard, E.J.A.: “Don’t Care” Modeling: A logical framework for developing predictive system models. In: Grumberg, O., Huth, M. (eds.) TACAS 2007. LNCS, vol. 4424, pp. 343–357. Springer, Heidelberg (2007)
Kugler, H., Segall, I.: Compositional Synthesis of Reactive Systems from Live Sequence Chart Specifications. In: Kowalewski, S., Philippou, A. (eds.) TACAS 2009. LNCS, vol. 5505, pp. 77–91. Springer, Heidelberg (2009)
Peter, I.S., Davidson, E.H.: A gene regulatory network controlling the embryonic specification of endoderm. Nature 474(7353) (2011)
Peter, I.S., Faure, E., Davidson, E.H.: Predictive computation of genomic logic processing functions in embryonic development. Proc. of the National Academy of Sciences 109(41) (2012)
Rabe, M.N., Wintersteiger, C.M., Kugler, H., Yordanov, B., Hamadi, Y.: Symbolic approximation of the bounded reachability probability in markov chains. In: QEST. LNCS, Springer (to appear, 2014)
Solar-Lezama, A., Rabbah, R.M., Bodík, R., Ebcioglu, K.: Programming by sketching for bit-streaming programs. In: PLDI. ACM (2005)
Srivastava, S., Gulwani, S., Foster, J.S.: From program verification to program synthesis. In: POPL. ACM (2010)
Yordanov, B., Wintersteiger, C.M., Hamadi, Y., Kugler, H.: Z34Bio: An SMT-based framework for analyzing biological computation. In: SMT (2013)
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Paoletti, N., Yordanov, B., Hamadi, Y., Wintersteiger, C.M., Kugler, H. (2014). Analyzing and Synthesizing Genomic Logic Functions. In: Biere, A., Bloem, R. (eds) Computer Aided Verification. CAV 2014. Lecture Notes in Computer Science, vol 8559. Springer, Cham. https://doi.org/10.1007/978-3-319-08867-9_23
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DOI: https://doi.org/10.1007/978-3-319-08867-9_23
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