@article{1823, abstract = {Abstract Drug combinations are increasingly important in disease treatments, for combating drug resistance, and for elucidating fundamental relationships in cell physiology. When drugs are combined, their individual effects on cells may be amplified or weakened. Such drug interactions are crucial for treatment efficacy, but their underlying mechanisms remain largely unknown. To uncover the causes of drug interactions, we developed a systematic approach based on precise quantification of the individual and joint effects of antibiotics on growth of genome-wide Escherichia coli gene deletion strains. We found that drug interactions between antibiotics representing the main modes of action are highly robust to genetic perturbation. This robustness is encapsulated in a general principle of bacterial growth, which enables the quantitative prediction of mutant growth rates under drug combinations. Rare violations of this principle exposed recurring cellular functions controlling drug interactions. In particular, we found that polysaccharide and ATP synthesis control multiple drug interactions with previously unexplained mechanisms, and small molecule adjuvants targeting these functions synthetically reshape drug interactions in predictable ways. These results provide a new conceptual framework for the design of multidrug combinations and suggest that there are universal mechanisms at the heart of most drug interactions. Synopsis A general principle of bacterial growth enables the prediction of mutant growth rates under drug combinations. Rare violations of this principle expose cellular functions that control drug interactions and can be targeted by small molecules to alter drug interactions in predictable ways. Drug interactions between antibiotics are highly robust to genetic perturbations. A general principle of bacterial growth enables the prediction of mutant growth rates under drug combinations. Rare violations of this principle expose cellular functions that control drug interactions. Diverse drug interactions are controlled by recurring cellular functions, including LPS synthesis and ATP synthesis. A general principle of bacterial growth enables the prediction of mutant growth rates under drug combinations. Rare violations of this principle expose cellular functions that control drug interactions and can be targeted by small molecules to alter drug interactions in predictable ways.}, author = {Chevereau, Guillaume and Bollenbach, Mark Tobias}, journal = {Molecular Systems Biology}, number = {4}, publisher = {Nature Publishing Group}, title = {{Systematic discovery of drug interaction mechanisms}}, doi = {10.15252/msb.20156098}, volume = {11}, year = {2015}, } @article{1824, abstract = {Condensation phenomena arise through a collective behaviour of particles. They are observed in both classical and quantum systems, ranging from the formation of traffic jams in mass transport models to the macroscopic occupation of the energetic ground state in ultra-cold bosonic gases (Bose-Einstein condensation). Recently, it has been shown that a driven and dissipative system of bosons may form multiple condensates. Which states become the condensates has, however, remained elusive thus far. The dynamics of this condensation are described by coupled birth-death processes, which also occur in evolutionary game theory. Here we apply concepts from evolutionary game theory to explain the formation of multiple condensates in such driven-dissipative bosonic systems. We show that the vanishing of relative entropy production determines their selection. The condensation proceeds exponentially fast, but the system never comes to rest. Instead, the occupation numbers of condensates may oscillate, as we demonstrate for a rock-paper-scissors game of condensates.}, author = {Knebel, Johannes and Weber, Markus and Krüger, Torben H and Frey, Erwin}, journal = {Nature Communications}, publisher = {Nature Publishing Group}, title = {{Evolutionary games of condensates in coupled birth-death processes}}, doi = {10.1038/ncomms7977}, volume = {6}, year = {2015}, } @article{1827, abstract = {Bow-tie or hourglass structure is a common architectural feature found in many biological systems. A bow-tie in a multi-layered structure occurs when intermediate layers have much fewer components than the input and output layers. Examples include metabolism where a handful of building blocks mediate between multiple input nutrients and multiple output biomass components, and signaling networks where information from numerous receptor types passes through a small set of signaling pathways to regulate multiple output genes. Little is known, however, about how bow-tie architectures evolve. Here, we address the evolution of bow-tie architectures using simulations of multi-layered systems evolving to fulfill a given input-output goal. We find that bow-ties spontaneously evolve when the information in the evolutionary goal can be compressed. Mathematically speaking, bow-ties evolve when the rank of the input-output matrix describing the evolutionary goal is deficient. The maximal compression possible (the rank of the goal) determines the size of the narrowest part of the network—that is the bow-tie. A further requirement is that a process is active to reduce the number of links in the network, such as product-rule mutations, otherwise a non-bow-tie solution is found in the evolutionary simulations. This offers a mechanism to understand a common architectural principle of biological systems, and a way to quantitate the effective rank of the goals under which they evolved.}, author = {Friedlander, Tamar and Mayo, Avraham and Tlusty, Tsvi and Alon, Uri}, journal = {PLoS Computational Biology}, number = {3}, publisher = {Public Library of Science}, title = {{Evolution of bow-tie architectures in biology}}, doi = {10.1371/journal.pcbi.1004055}, volume = {11}, year = {2015}, } @article{1828, abstract = {We construct a non-linear Markov process connected with a biological model of a bacterial genome recombination. The description of invariant measures of this process gives us the solution of one problem in elementary probability theory.}, author = {Akopyan, Arseniy and Pirogov, Sergey and Rybko, Aleksandr}, journal = {Journal of Statistical Physics}, number = {1}, pages = {163 -- 167}, publisher = {Springer}, title = {{Invariant measures of genetic recombination process}}, doi = {10.1007/s10955-015-1238-5}, volume = {160}, year = {2015}, } @article{1830, abstract = {To prevent epidemics, insect societies have evolved collective disease defences that are highly effective at curing exposed individuals and limiting disease transmission to healthy group members. Grooming is an important sanitary behaviour—either performed towards oneself (self-grooming) or towards others (allogrooming)—to remove infectious agents from the body surface of exposed individuals, but at the risk of disease contraction by the groomer. We use garden ants (Lasius neglectus) and the fungal pathogen Metarhizium as a model system to study how pathogen presence affects self-grooming and allogrooming between exposed and healthy individuals. We develop an epidemiological SIS model to explore how experimentally observed grooming patterns affect disease spread within the colony, thereby providing a direct link between the expression and direction of sanitary behaviours, and their effects on colony-level epidemiology. We find that fungus-exposed ants increase self-grooming, while simultaneously decreasing allogrooming. This behavioural modulation seems universally adaptive and is predicted to contain disease spread in a great variety of host–pathogen systems. In contrast, allogrooming directed towards pathogen-exposed individuals might both increase and decrease disease risk. Our model reveals that the effect of allogrooming depends on the balance between pathogen infectiousness and efficiency of social host defences, which are likely to vary across host–pathogen systems.}, author = {Theis, Fabian and Ugelvig, Line V and Marr, Carsten and Cremer, Sylvia}, issn = {1471-2970}, journal = {Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences}, number = {1669}, publisher = {Royal Society, The}, title = {{Opposing effects of allogrooming on disease transmission in ant societies}}, doi = {10.1098/rstb.2014.0108}, volume = {370}, year = {2015}, } @article{1831, abstract = {This paper introduces a theme issue presenting the latest developments in research on the impacts of sociality on health and fitness. The articles that follow cover research on societies ranging from insects to humans. Variation in measures of fitness (i.e. survival and reproduction) has been linked to various aspects of sociality in humans and animals alike, and variability in individual health and condition has been recognized as a key mediator of these relationships. Viewed from a broad evolutionary perspective, the evolutionary transitions from a solitary lifestyle to group living have resulted in several new health-related costs and benefits of sociality. Social transmission of parasites within groups represents a major cost of group living, but some behavioural mechanisms, such as grooming, have evolved repeatedly to reduce this cost. Group living also has created novel costs in terms of altered susceptibility to infectious and non-infectious disease as a result of the unavoidable physiological consequences of social competition and integration, which are partly alleviated by social buffering in some vertebrates. Here, we define the relevant aspects of sociality, summarize their health-related costs and benefits, and discuss possible fitness measures in different study systems. Given the pervasive effects of social factors on health and fitness, we propose a synthesis of existing conceptual approaches in disease ecology, ecological immunology and behavioural neurosciences by adding sociality as a key factor, with the goal to generate a broader framework for organismal integration of health-related research.}, author = {Kappeler, Peter and Cremer, Sylvia and Nunn, Charles}, journal = {Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences}, number = {1669}, publisher = {Royal Society}, title = {{Sociality and health: Impacts of sociality on disease susceptibility and transmission in animal and human societies}}, doi = {10.1098/rstb.2014.0116}, volume = {370}, year = {2015}, } @article{1832, abstract = {Linearizability of concurrent data structures is usually proved by monolithic simulation arguments relying on the identification of the so-called linearization points. Regrettably, such proofs, whether manual or automatic, are often complicated and scale poorly to advanced non-blocking concurrency patterns, such as helping and optimistic updates. In response, we propose a more modular way of checking linearizability of concurrent queue algorithms that does not involve identifying linearization points. We reduce the task of proving linearizability with respect to the queue specification to establishing four basic properties, each of which can be proved independently by simpler arguments. As a demonstration of our approach, we verify the Herlihy and Wing queue, an algorithm that is challenging to verify by a simulation proof. }, author = {Chakraborty, Soham and Henzinger, Thomas A and Sezgin, Ali and Vafeiadis, Viktor}, journal = {Logical Methods in Computer Science}, number = {1}, publisher = {International Federation of Computational Logic}, title = {{Aspect-oriented linearizability proofs}}, doi = {10.2168/LMCS-11(1:20)2015}, volume = {11}, year = {2015}, } @inbook{18326, abstract = {Nonrigid shapes are ubiquitous in nature and are encountered at all levels of life, from macro to nano. The need to model such shapes and understand their behavior arises in many applications in imaging sciences, pattern recognition, computer vision, and computer graphics. Of particular importance is understanding which properties of the shape are attributed to deformations and which are invariant, i.e., remain unchanged. This chapter presents an approach to nonrigid shapes from the point of view of metric geometry. Modeling shapes as metric spaces, one can pose the problem of shape similarity as the similarity of metric spaces and harness tools from theoretical metric geometry for the computation of such a similarity.}, author = {Bronstein, Alexander and Bronstein, Michael M.}, booktitle = {Handbook of Mathematical Methods in Imaging}, editor = {Scherzer, Otmar}, isbn = {9781493907892}, pages = {1859--1908}, publisher = {Springer Nature}, title = {{Manifold Intrinsic Similarity}}, doi = {10.1007/978-1-4939-0790-8_57}, year = {2015}, } @inbook{18327, abstract = {Source separation is a widely studied problem in signal processing. Despite the permanent progress reported in the literature it is still considered a significant challenge. This chapter first reviews the use of non-negative matrix factorization (NMF) algorithms for solving source separation problems, and proposes a new way for the supervised training in NMF. Matrix factorization methods have received a lot of attention in recent year in the audio processing community, producing particularly good results in source separation. Traditionally, NMF algorithms consist of two separate stages: a training stage, in which a generative model is learned; and a testing stage in which the pre-learned model is used in a high level task such as enhancement, separation, or classification. As an alternative, we propose a task-supervised NMF method for the adaptation of the basis spectra learned in the first stage to enhance the performance on the specific task used in the second stage. We cast this problem as a bilevel optimization program efficiently solved via stochastic gradient descent. The proposed approach is general enough to handle sparsity priors of the activations, and allow non-Euclidean data terms such as β-divergences. The framework is evaluated on speech enhancement.}, author = {Sprechmann, Pablo and Bronstein, Alexander and Sapiro, Guillermo}, booktitle = {Excursions in Harmonic Analysis, Volumne 4}, isbn = {9783319201870}, issn = {2296-5017}, pages = {407--420}, publisher = {Springer Nature}, title = {{Supervised non-negative matrix factorization for audio source separation}}, doi = {10.1007/978-3-319-20188-7_16}, year = {2015}, } @article{1834, abstract = {Huge body of evidences demonstrated that volatile anesthetics affect the hippocampal neurogenesis and neurocognitive functions, and most of them showed impairment at anesthetic dose. Here, we investigated the effect of low dose (1.8%) sevoflurane on hippocampal neurogenesis and dentate gyrus-dependent learning. Neonatal rats at postnatal day 4 to 6 (P4-6) were treated with 1.8% sevoflurane for 6 hours. Neurogenesis was quantified by bromodeoxyuridine labeling and electrophysiology recording. Four and seven weeks after treatment, the Morris water maze and contextual-fear discrimination learning tests were performed to determine the influence on spatial learning and pattern separation. A 6-hour treatment with 1.8% sevoflurane promoted hippocampal neurogenesis and increased the survival of newborn cells and the proportion of immature granular cells in the dentate gyrus of neonatal rats. Sevoflurane-treated rats performed better during the training days of the Morris water maze test and in contextual-fear discrimination learning test. These results suggest that a subanesthetic dose of sevoflurane promotes hippocampal neurogenesis in neonatal rats and facilitates their performance in dentate gyrus-dependent learning tasks.}, author = {Chen, Chong and Wang, Chao and Zhao, Xuan and Zhou, Tao and Xu, Dao and Wang, Zhi and Wang, Ying}, journal = {ASN Neuro}, number = {2}, publisher = {SAGE Publications}, title = {{Low-dose sevoflurane promoteshippocampal neurogenesis and facilitates the development of dentate gyrus-dependent learning in neonatal rats}}, doi = {10.1177/1759091415575845}, volume = {7}, year = {2015}, } @inproceedings{1835, abstract = {The behaviour of gene regulatory networks (GRNs) is typically analysed using simulation-based statistical testing-like methods. In this paper, we demonstrate that we can replace this approach by a formal verification-like method that gives higher assurance and scalability. We focus on Wagner’s weighted GRN model with varying weights, which is used in evolutionary biology. In the model, weight parameters represent the gene interaction strength that may change due to genetic mutations. For a property of interest, we synthesise the constraints over the parameter space that represent the set of GRNs satisfying the property. We experimentally show that our parameter synthesis procedure computes the mutational robustness of GRNs –an important problem of interest in evolutionary biology– more efficiently than the classical simulation method. We specify the property in linear temporal logics. We employ symbolic bounded model checking and SMT solving to compute the space of GRNs that satisfy the property, which amounts to synthesizing a set of linear constraints on the weights.}, author = {Giacobbe, Mirco and Guet, Calin C and Gupta, Ashutosh and Henzinger, Thomas A and Paixao, Tiago and Petrov, Tatjana}, location = {London, United Kingdom}, pages = {469 -- 483}, publisher = {Springer}, title = {{Model checking gene regulatory networks}}, doi = {10.1007/978-3-662-46681-0_47}, volume = {9035}, year = {2015}, } @inproceedings{1836, abstract = {In the standard framework for worst-case execution time (WCET) analysis of programs, the main data structure is a single instance of integer linear programming (ILP) that represents the whole program. The instance of this NP-hard problem must be solved to find an estimate forWCET, and it must be refined if the estimate is not tight.We propose a new framework for WCET analysis, based on abstract segment trees (ASTs) as the main data structure. The ASTs have two advantages. First, they allow computing WCET by solving a number of independent small ILP instances. Second, ASTs store more expressive constraints, thus enabling a more efficient and precise refinement procedure. In order to realize our framework algorithmically, we develop an algorithm for WCET estimation on ASTs, and we develop an interpolation-based counterexample-guided refinement scheme for ASTs. Furthermore, we extend our framework to obtain parametric estimates of WCET. We experimentally evaluate our approach on a set of examples from WCET benchmark suites and linear-algebra packages. We show that our analysis, with comparable effort, provides WCET estimates that in many cases significantly improve those computed by existing tools.}, author = {Cerny, Pavol and Henzinger, Thomas A and Kovács, Laura and Radhakrishna, Arjun and Zwirchmayr, Jakob}, location = {London, United Kingdom}, pages = {105 -- 131}, publisher = {Springer}, title = {{Segment abstraction for worst-case execution time analysis}}, doi = {10.1007/978-3-662-46669-8_5}, volume = {9032}, year = {2015}, } @article{18365, abstract = {Yeast cells with DNA damage avoid respiration, presumably because products of oxidative metabolism can be harmful to DNA. We show that DNA damage inhibits the activity of the Snf1 (AMP-activated) protein kinase (AMPK), which activates expression of genes required for respiration. Glucose and DNA damage upregulate SUMOylation of Snf1, catalyzed by the SUMO E3 ligase Mms21, which inhibits SNF1 activity. The DNA damage checkpoint kinases Mec1/ATR and Tel1/ATM, as well as the nutrient-sensing protein kinase A (PKA), regulate Mms21 activity toward Snf1. Mec1 and Tel1 are required for two SNF1-regulated processes—glucose sensing and ADH2 gene expression—even without exogenous genotoxic stress. Our results imply that inhibition of Snf1 by SUMOylation is a mechanism by which cells lower their respiration in response to DNA damage. This raises the possibility that activation of DNA damage checkpoint mechanisms could contribute to aerobic fermentation (Warburg effect), a hallmark of cancer cells.}, author = {Simpson-Lavy, Kobi J. and Bronstein, Alexander and Kupiec, Martin and Johnston, Mark}, issn = {2211-1247}, journal = {Cell Reports}, number = {11}, pages = {1865--1875}, publisher = {Elsevier}, title = {{Cross-talk between carbon cetabolism and the DNA camage response in S. cerevisiae}}, doi = {10.1016/j.celrep.2015.08.025}, volume = {12}, year = {2015}, } @article{1837, abstract = {Transition to turbulence in straight pipes occurs in spite of the linear stability of the laminar Hagen-Poiseuille flow if both the amplitude of flow perturbations and the Reynolds number Re exceed a minimum threshold (subcritical transition). As the pipe curvature increases, centrifugal effects become important, modifying the basic flow as well as the most unstable linear modes. If the curvature (tube-to-coiling diameter d/D) is sufficiently large, a Hopf bifurcation (supercritical instability) is encountered before turbulence can be excited (subcritical instability). We trace the instability thresholds in the Re - d/D parameter space in the range 0.01 ≤ d/D\ ≤ 0.1 by means of laser-Doppler velocimetry and determine the point where the subcritical and supercritical instabilities meet. Two different experimental set-ups are used: a closed system where the pipe forms an axisymmetric torus and an open system employing a helical pipe. Implications for the measurement of friction factors in curved pipes are discussed.}, author = {Kühnen, Jakob and Braunshier, P and Schwegel, M and Kuhlmann, Hendrik and Hof, Björn}, journal = {Journal of Fluid Mechanics}, number = {5}, publisher = {Cambridge University Press}, title = {{Subcritical versus supercritical transition to turbulence in curved pipes}}, doi = {10.1017/jfm.2015.184}, volume = {770}, year = {2015}, } @article{18371, abstract = {We consider the problem of exact and inexact matching of weighted undirected graphs, in which a bijective correspondence is sought to minimize a quadratic weight disagreement. This computationally challenging problem is often relaxed as a convex quadratic program, in which the space of permutations is replaced by the space of doubly stochastic matrices. However, the applicability of such a relaxation is poorly understood. We define a broad class of friendly graphs characterized by an easily verifiable spectral property. We prove that for friendly graphs, the convex relaxation is guaranteed to find the exact isomorphism or certify its inexistence. This result is further extended to approximately isomorphic graphs, for which we develop an explicit bound on the amount of weight disagreement under which the relaxation is guaranteed to find the globally optimal approximate isomorphism. We also show that in many cases, the graph matching problem can be further harmlessly relaxed to a convex quadratic program with only n separable linear equality constraints, which is substantially more efficient than the standard relaxation involving 2n equality and n2 inequality constraints. Finally, we show that our results are still valid for unfriendly graphs if additional information in the form of seeds or attributes is allowed, with the latter satisfying an easy to verify spectral characteristic.}, author = {Aflalo, Yonathan and Bronstein, Alexander and Kimmel, Ron}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {10}, pages = {2942--2947}, publisher = {National Academy of Sciences}, title = {{On convex relaxation of graph isomorphism}}, doi = {10.1073/pnas.1401651112}, volume = {112}, year = {2015}, } @inproceedings{1838, abstract = {Synthesis of program parts is particularly useful for concurrent systems. However, most approaches do not support common design tasks, like modifying a single process without having to re-synthesize or verify the whole system. Assume-guarantee synthesis (AGS) provides robustness against modifications of system parts, but thus far has been limited to the perfect information setting. This means that local variables cannot be hidden from other processes, which renders synthesis results cumbersome or even impossible to realize.We resolve this shortcoming by defining AGS under partial information. We analyze the complexity and decidability in different settings, showing that the problem has a high worstcase complexity and is undecidable in many interesting cases. Based on these observations, we present a pragmatic algorithm based on bounded synthesis, and demonstrate its practical applicability on several examples.}, author = {Bloem, Roderick and Chatterjee, Krishnendu and Jacobs, Swen and Könighofer, Robert}, location = {London, United Kingdom}, pages = {517 -- 532}, publisher = {Springer}, title = {{Assume-guarantee synthesis for concurrent reactive programs with partial information}}, doi = {10.1007/978-3-662-46681-0_50}, volume = {9035}, year = {2015}, } @inproceedings{18380, abstract = {This work presents a novel approach for detecting inliers in a given set of correspondences (matches). It does so without explicitly identifying any consensus set, based on a method for inlier rate estimation (IRE). Given such an estimator for the inlier rate, we also present an algorithm that detects a globally optimal transformation. We provide a theoretical analysis of the IRE method using a stochastic generative model on the continuous spaces of matches and transformations. This model allows rigorous investigation of the limits of our IRE method for the case of 2D-translation, further giving bounds and insights for the more general case. Our theoretical analysis is validated empirically and is shown to hold in practice for the more general case of 2D-affinities. In addition, we show that the combined framework works on challenging cases of 2D-homography estimation, with very few and possibly noisy inliers, where RANSAC generally fails.}, author = {Litman, Roee and Korman, Simon and Bronstein, Alexander and Avidan, Shai}, booktitle = {2015 IEEE Conference on Computer Vision and Pattern Recognition (CVPR)}, isbn = {9781467369640}, issn = {1063-6919}, location = {Boston, MA, United States}, publisher = {IEEE}, title = {{Inverting RANSAC: Global model detection via inlier rate estimation}}, doi = {10.1109/cvpr.2015.7299161}, year = {2015}, } @inproceedings{18387, abstract = {Sparse models in dictionary learning have been successfully applied in a wide variety of machine learning and computer vision problems, and have also recently been of increasing research interest. Another interesting related problem based on a linear equality constraint, namely the sparse null space problem (SNS), first appeared in 1986, and has since inspired results on sparse basis pursuit. In this paper, we investigate the relation between the SNS problem and the analysis dictionary learning problem, and show that the SNS problem plays a central role, and may be utilized to solve dictionary learning problems. Moreover, we propose an efficient algorithm of sparse null space basis pursuit, and extend it to a solution of analysis dictionary learning. Experimental results on numerical synthetic data and real-world data are further presented to validate the performance of our method.}, author = {Bian, Xiao and Krim, Hamid and Bronstein, Alexander and Dai, Liyi}, booktitle = {2015 IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP)}, issn = {2379-190X}, location = {South Brisbane, QLD, Australia}, publisher = {IEEE}, title = {{Sparse null space basis pursuit and analysis dictionary learning for high-dimensional data analysis}}, doi = {10.1109/icassp.2015.7178678}, year = {2015}, } @inproceedings{1839, abstract = {We present MultiGain, a tool to synthesize strategies for Markov decision processes (MDPs) with multiple mean-payoff objectives. Our models are described in PRISM, and our tool uses the existing interface and simulator of PRISM. Our tool extends PRISM by adding novel algorithms for multiple mean-payoff objectives, and also provides features such as (i) generating strategies and exploring them for simulation, and checking them with respect to other properties; and (ii) generating an approximate Pareto curve for two mean-payoff objectives. In addition, we present a new practical algorithm for the analysis of MDPs with multiple mean-payoff objectives under memoryless strategies.}, author = {Brázdil, Tomáš and Chatterjee, Krishnendu and Forejt, Vojtěch and Kučera, Antonín}, location = {London, United Kingdom}, pages = {181 -- 187}, publisher = {Springer}, title = {{Multigain: A controller synthesis tool for MDPs with multiple mean-payoff objectives}}, doi = {10.1007/978-3-662-46681-0_12}, volume = {9035}, year = {2015}, } @article{1840, abstract = {In this paper, we present a method for reducing a regular, discrete-time Markov chain (DTMC) to another DTMC with a given, typically much smaller number of states. The cost of reduction is defined as the Kullback-Leibler divergence rate between a projection of the original process through a partition function and a DTMC on the correspondingly partitioned state space. Finding the reduced model with minimal cost is computationally expensive, as it requires an exhaustive search among all state space partitions, and an exact evaluation of the reduction cost for each candidate partition. Our approach deals with the latter problem by minimizing an upper bound on the reduction cost instead of minimizing the exact cost. The proposed upper bound is easy to compute and it is tight if the original chain is lumpable with respect to the partition. Then, we express the problem in the form of information bottleneck optimization, and propose using the agglomerative information bottleneck algorithm for searching a suboptimal partition greedily, rather than exhaustively. The theory is illustrated with examples and one application scenario in the context of modeling bio-molecular interactions.}, author = {Geiger, Bernhard and Petrov, Tatjana and Kubin, Gernot and Koeppl, Heinz}, issn = {0018-9286}, journal = {IEEE Transactions on Automatic Control}, number = {4}, pages = {1010 -- 1022}, publisher = {IEEE}, title = {{Optimal Kullback-Leibler aggregation via information bottleneck}}, doi = {10.1109/TAC.2014.2364971}, volume = {60}, year = {2015}, }