Christian L. Müller


Christian L. Müller

Research Interests

I am a research scientist and project leader in computational statistics and optimization at the Flatiron Institute.

I am interested in developing novel computational statistical tools and their applications in microbial ecology and biology.

On the computational side I am interested in:

  • High-dimensional variable selection schemes such as the LASSO and the TREX
  • Black-box (a.k.a. gradient-free, derivative-free, direct search) optimization and sampling algorithms such as CMA-ES, Gaussian Adaptation, and adaptive MCMC
  • Proximal algorithms and their application in statistics
  • Statistical and spectral methods to analyze complex networks
  • Statistical tools to describe energy and fitness landscapes

On the biological side my research interests revolve around:

  • Inference of microbial interaction networks from 16S rRNA data
  • Inference of transcriptional regulatory networks from high-throughput measurements
  • Robustness of parameter spaces in biological networks 
  • Protein conformation spaces and prediction of deleterious mutations in proteins

A recent CV can be found here (pdf).

My ResearchGate profile can be found here.

My personal github repository is here.

We are organizing  the second workshop on statistical and computational challenges in microbiome research which will take place on the 16th-17th of February 2017 at the Broad Institute, Cambridge. Information and registration can be found here.

We have organized a workshop on statistical and computational challenges in microbiome research on the 25th-26th of February 2016 at the Simons Foundation, New York. Further information can be found here.

Please find below a list of representative publications. If you’re interested in working with me at SCDA, I am currently having two research scientist positions available. Please contact me via cmueller[at] for further information.

Selected Publications

Recent manuscripts under review/in preparation

Asmus J,  Müller CL, Sbalzarini IF. Approximate Design Centering and Robustness Quantification of Biological and Electronic Networks. submitted

Äijö, T, Müller CL, Bonneau R, Temporal probabilistic modeling of bacterial compositions derived from 16S rRNA sequencing.  [code]

Müller CL, Bonneau R, Kurtz ZD. Generalized Stability Approach for Regularized Graphical Models. [code]

Bien J, Gaynanova I, Lederer J, Müller CL. Non-convex Global Minimization and False Discovery Rate Control for the TREX. arXiv preprint arXiv:1604.06815  [code]

Bien J, Gaynanova I, Lederer J, Müller CL. Theory for the . In preparation 2015 [overview]

Lederer J, Müller CL. Topology adaptive graph estimation in high dimensions. arXiv preprint arXiv:1410.7279, 2014. [code]

Cázáls F, Robert C, Roth A, Müller CL, Towards Morse Theory for Point Cloud Data. HAL preprint, 2013.

Recent highlights

Combettes PL, Müller CL. Perspective Functions: Proximal Calculus and Applications in High Dimensional Statistics. J. Math. Anal. Appl., 2017  [code]

Raviram R, Rocha PP, Müller CL, Miraldi ER, Fu Y, Swanzey E, Badri S, Proudhon C, Snetkova V, Bonneau R, Skok JA. 4C-ker: A method to reproducibly identify genome-wide interactions captured by 4C-Seq experiments. PLoS Comput Biol 2016; 12(3): e1004780.[code]

Baugh EH, Simmons-Edler R, Müller CL, Alford RF, Volfovsky N, Lash AE, Bonneau R. Robust Classification of Protein Variation Using Structural Modeling and Large-Scale Data Integration Nucl. Acids Res. 2016; 44 (6): 2501-2513[code]

High-dimensional statistics

Hill SM et al., HPN-DREAM Consortium, Inferring causal molecular networks: empirical assessment through a community-based effort. Nature Methods, 2016.

Lam KY, Westrick, ZM, Müller CL, Christiaen L, Bonneau R, Fused Regression for multi-source regulatory network inference. PLoS Comput Biol. 2016;12(12):e1005157.

Kurtz ZD*, Müller CL*, Miraldi ER*, Littman DR, Blaser MJ, Bonneau RA. Sparse and compositionally robust inference of microbial ecological networks. PLoS Comput Biol. 2015;11(5):e1004226  (* joint first authors) [code]

Lederer J*, Müller CL*. Don’t fall for tuning parameters: Tuning-free variable selection in high dimensions with the TREX. Proceedings of the Twenty-Ninth AAAI Conference on Artificial Intelligence, 2015. (* joint first authors).  [code]

Optimization and Monte Carlo sampling

Stich SU, Müller CL, Gärtner B. Variable Metric Random Pursuit. Math Program A, May 24, 2015.

Müller CL. Stochastic methods for single objective global optimization. In: AAIA Computational Intelligence in Aerospace Sciences, 2014. 63-112.

Stich SU, Müller CL, Gärtner B. Optimization of convex functions with Random Pursuit. SIAM J Optim 2013;23(2):1284-1309.

Müller CL, Sbalzarini IF. Gaussian adaptation revisited: an entropic view on covariance matrix adaptation. In: Di Chio C, Cagnoni S, Cotta, C, et al., Applications of Evolutionary Computation: EvoApplications 2010. Berlin and Heidelberg, Germany: Springer; 2010:432-441. [code]

Müller CL, Baumgartner B, Sbalzarini IF. Particle swarm CMA evolution strategy for the optimization of multi-funnel landscapes. Proc. IEEE Congress on Evolutionary Computation (CEC), May 18-21, 2009; Trondheim, Norway[code]

Fitness and energy landscapes

Müller CL, Sbalzarini IF. Energy landscapes of atomic clusters as black box optimization benchmarks. Evol Comput. 2012;20(4):543R573. [code]

Müller CL, Sbalzarini IF. Global characterization of the CEC 2005 fitness landscapes using fitness-distance analysis. In: Di Chio C, Cagnoni S, Cotta C, et al., eds. Applications of Evolutionary Computation: EvoApplications 2011. Berlin and Heidelberg, Germany: Springer; 2011:294-303.

Biological data analysis and modeling

Mahana, D, Trent CM, Kurtz, ZD, Bokulich, NA, Battaglia T,Chung, J, Müller CL, Li, H, Bonneau RA, Blaser MJ. Antibiotic perturbation of the murine gut microbiome enhances the adiposity, insulin resistance, and liver disease associated with high-fat diet Genome Medicine, 8:48, 2016.

Plessis A, Hafemeister C, Wilkins O, Gonzaga ZJ, Meyer RS, Pires I, Müller CL, Septiningsih EM, Bonneau R, Purugganan M. Multiple abiotic stimuli are integrated in the regulation of rice gene expression under field conditions. eLIFE 2015.

Tchourine K*, Poultney CS*, Wang L*, Silva GM, Manohar S, Mueller CL, Bonneau R, and Vogel C. One third of dynamic protein expression profiles can be predicted by a simple rate equation. Mol Biosyst. 2014;10:2850-2862. (* joint first authors)

Billerbeck S, Calles B, Müller CL, de Lorenzo V, Panke S. Towards Functional Orthogonalisation of Protein Complexes: Individualisation of GroEL Monomers Leads to Distinct Quasihomogeneous Single Rings. Chembiochem. 2013;14(17):2310-2321.

Müller CL, Sbalzarini IF, van Gunsteren WF, Zagrovic B, Hünenberger PH. In the eye of the beholder: inhomogeneous distribution of high resolution shapes within the random walk ensemble. J Chem Phys. 2009;130(21):214904.


Müller CL. Black-box landscapes: characterization, optimization, sampling and application to geometric configuration problems [Dissertation]. Zürich, Switzerland: ETH Zürich; 2010.

Müller CL. Parameter sensitivity analysis in behavioral and analog circuit simulations of neuro-fuzzy models [Diploma thesis]. Tübingen, Germany: University of Tübingen; 2006.

Müller CL. die erde dreht sich zu laut: gedichte von der schwedischen oberfläche [Certificate thesis]. Tübingen, Germany: University of Tübingen; 2005.

Müller CL. High order accurate numerical solution of the linearized Euler equations for sound propagation in the atmosphere [Master’s thesis]. Uppsala, Sweden: Uppsala University, 2004.

Active Collaborations

Jacob Bien, Department BSCB, Cornell University, USA, High-dimensional statistics.

Martin Blaser, New York School of Medicine, USA, Microbiome data analysis.

Patrick Combettes, NC State, USA, Proximal algorithms.

Johannes. Lederer, Statistics Department, UW Seattle, USA, High-dimensional statistics.

Ivo F. Sbalzarini, Max-Planck-Institute for Cell Biology, Dresden, Germany, Markov Chain Monte Carlo, Optimization.

Thomas J. Fuchs, Memorial Sloan Kettering Cancer Center, New York, USA, Approximate Bayesian Computation .

Frederic Cazals, INRIA Sophia-Antipolis, Sophia-Antipolis, France, Computational topological analysis of high-dimensional sampled landscapes.

Bojan Zagrovic, Max F. Perutz Laboratories and University of Vienna, Vienna, Austria, Conformation space analysis of chain molecules.

Co-Principal Supervision of Students

PhD theses (since 2010):

Sebastian Stich (completed, with Dr. Bernd Gärtner, ETH Zürich) now at UC Louvain, Belgium

Josefine Asmus (ongoing, with Dr. Ivo F. Sbalzarini, MPI Dresden)

Master/diploma theses (2006-2010, ETH Zürich):

Ana Tusek, Benedikt Baumgartner, Christian Fiegl, Georg Ofenbeck, Markus König, Daniel Zünd, (with Ivo F. Sbalzarini), Thomas Lampart (with Peter Widmayer)

Bachelor/semester theses (2006-2010, ETH Zürich):

Johannes Lederer, Yannick Misteli, Patrick Plattner (with Ivo F. Sbalzarini)

Mentoring  of Graduate Students (since 2013, NYU):

Evan Baugh, Zachary Kurtz, Ramya Raviram

Josh Fass (Principal supervisor John Chodera, MSKCC)