A highly efficient multicore algorithm for clustering extremely large datasets
 Johann M Kraus^{1, 2} and
 Hans A Kestler^{1, 2}Email author
DOI: 10.1186/1471210511169
© Kraus and Kestler; licensee BioMed Central Ltd. 2010
Received: 1 September 2009
Accepted: 6 April 2010
Published: 6 April 2010
Abstract
Background
In recent years, the demand for computational power in computational biology has increased due to rapidly growing data sets from microarray and other highthroughput technologies. This demand is likely to increase. Standard algorithms for analyzing data, such as cluster algorithms, need to be parallelized for fast processing. Unfortunately, most approaches for parallelizing algorithms largely rely on network communication protocols connecting and requiring multiple computers. One answer to this problem is to utilize the intrinsic capabilities in current multicore hardware to distribute the tasks among the different cores of one computer.
Results
We introduce a multicore parallelization of the kmeans and kmodes cluster algorithms based on the design principles of transactional memory for clustering gene expression microarray type data and categorial SNP data. Our new shared memory parallel algorithms show to be highly efficient. We demonstrate their computational power and show their utility in cluster stability and sensitivity analysis employing repeated runs with slightly changed parameters. Computation speed of our Java based algorithm was increased by a factor of 10 for large data sets while preserving computational accuracy compared to singlecore implementations and a recently published network based parallelization.
Conclusions
Most desktop computers and even notebooks provide at least dualcore processors. Our multicore algorithms show that using modern algorithmic concepts, parallelization makes it possible to perform even such laborious tasks as cluster sensitivity and cluster number estimation on the laboratory computer.
Background
The advent of highthroughput methods to life sciences has increased the need for computerintensive applications to analyze large data sets in the laboratory. Currently, the field of bioinformatics is confronted with data sets containing thousands of samples and up to millions of features, e.g. gene expression arrays and genomewide association studies using single nucleotide polymorphism (SNP) chips. To explore these data sets that are too large for manual analysis, machine learning methods are employed [1]. Among them, cluster algorithms partition objects into different groups that have similar characteristics. These methods have already become a valuable tool to detect associations between combinations of SNP markers and diseases and for the selection of tag SNPs [2, 3]. Not only here, the size of the generated data sets has grown up to 1000000 markers per chip. The demand for performing these computerintensive applications is likely to increase even further for two reasons: First, with the popularity of nextgeneration sequencing methods rising, the number of measurements per sample will soar. Second, the need to assist researchers in answering questions such as "How many groups are in my data?" or "How robust is the identified clustering?" will increase. Cluster number estimation techniques address these types of questions by repeated use of a cluster algorithm with slightly different initializations or data sets, ultimately performing a sensitivity analysis.
In the past, computing speeds doubled approximately every 2 years via increasing clock speeds, giving software a "free ride" to better performance [4]. This is now over, and such automatic performance improvements are no longer possible. As clock speeds are stalling, the increase in computational power is now due to the rapid increase of the number of cores per processor. This makes parallel computation a necessity for the timeconsuming analyses in the laboratory. Generally, two parallelization schemes are available. The first is based on a network of computers or computing nodes. The idea of such a masterslave parallelization is to parallelize independent tasks using a network of one master and several slave computers. While there is no possibility for communication between the slaves, this approach best fits scenarios where the same serial algorithm is started several times on different relatively small data sets or different analyses are calculated in parallel on the same data set. Data set size matters here, as distribution of large data sets is time consuming and requires all computers to have the appropriate memory configuration. The second approach called shared memory parallelization is used to parallelize the implementation of an algorithm itself. This is an intrinsic parallelization via different interwoven subprocesses (threads) on a single multicore computer accessing a common memory, and requires a redesign of the original serial algorithm.
Masterslave parallelization
Masterslave parallelization is heavily used by computer clusters or supercomputers. The Message Passing Interface (MPI) [5] protocol is the dominant model in highperformance computing. Without shared memory the compute nodes are restricted to process independent tasks. As long as the loadbalancing of the compute nodes is well handled, the parallelization of a complex simulation scales linearly with the number of compute nodes. In contrast to massive parallel simulation runs of complex algorithms, masterslave parallelization is also used for parallelizing algorithms. For this task, a large dataset is usually first split into smaller pieces. The subsets are then distributed through a computer network and each compute node solves a subtask for its subset. Finally, all results are transferred back to the master computer, which combines them to a global result. The user interacts with the hardware cluster through the master computer or via a webinterface. However, in addition to hardware requirements, such as minimal amount of memory that are imposed on each compute node, the effort of distributing the data and communicating with nodes of the computer network restricts the speedup achievable with this method. An approach similar to MPI by Kraj et al. [6] uses webservices for parallel distribution of code, which can reduce the effort for administrating a computer cluster, but is platformdependent. A very popular programming environment in the bioinformatics and biostatistics community is R [7, 8]. In recent years several packages (snow, snowfall, nws, multicore) have been developed that enable masterslave parallelized R programs to run on computer cluster platforms or multicore computers, see Hill et al. [9] for an overview of packages for parallel programming in R.
Shared memory parallelization
Today most desktop computers and even notebooks provide at least dualcore processors. Compared to masterslave parallelization, developing sharedmemory software reduces the overhead of communicating through a network. Despite its performance in parallelizing algorithms, shared memory parallelization is not yet regularly applied during development of scientific software. For instance, shared memory programming with R is currently rather limited to a small number of parallelized functions [9].
Sharedmemory programming concepts like the Open MultiProcessing (Open MP) [10] are closely linked to thread programming. A sequential program is decomposed into several tasks, which are then processed as threads. The concept of thread programming is available in many programming languages like C (PThreads or OpenMP threads), Java (JThreads), or Fortran (OpenMP threads) and on many multicore platforms [11]. Threads are refinements of a process that usually share the same memory and can be separately and simultaneously processed, but can also be used to imitate masterslave parallelization by avoiding access to shared memory [11]. Due to the mostly used shared memory concept, communication between threads is much faster than the communication of processes through sockets. In a multicore parallelization setting there is no need for network communication, as all threads run on the same computer. On the other hand, as every thread has access to all objects on the heap there is a need for concurrency control [12]. Concurrency control ensures that software can be parallelized without violating data integrity. The most prominent approach for managing concurrent programs is the use of locks [10]. Locking and synchronizing ensures that changes to the states of the data are coordinated, but implementing threadsafe programs using locks can be fatally errorprone [13]. Problems might occur when using too few locks, too many locks, wrong locks, or locks in the wrong order [14]. For instance an implementation may cause deadlocks, where two processes are waiting for each other to first release a resource.
In the following we describe a new multicore parallel cluster algorithm (McKmeans) that runs in shared memory, and avoids locks for concurrency control. Benchmark results on artificial and real microarray data are shown. The utility of our computerintensive cluster method is further demonstrated on cluster sensitivity and cluster number estimation of highdimensional gene expression and SNP data.
Implementation
Multicore kmeans/kmodes clustering
The basic clustering task can be formulated as an optimization problem:
Partitional cluster analysis
For a fixed number of groups k find that partition P(k) of a data set X out of the set of all possible partitions Φ (X, k) for which a chosen objective function f: Φ (X, k) → ℝ^{+} is optimized. For all possible partitions with k clusters compute the value of the objective function f. The partition with the best value is the set of clusters sought.
Existing algorithms provide different heuristics for this search problem. kmeans is probably one of the most popular of these partitional cluster algorithms [16]. The following listing shows the pseudocode for the kmeans algorithm:
Function kmeans
Input: X = {x_1, ..., x_n} (Data to be clustered)
k (Number of clusters)
Output: C = {c_1, ..., c_k} (Cluster centroids)
m: X>C (Cluster assignments)
Initialize C (e. g. random selection from X)
While C has changed
For each x_i in X
m(x_i) = argmin_j distance (x_i, c_j)
End
For each c_j in C
c_j = centroid ({x_i  m(x_i) = j})
End
End
Given a number k, the kmeans algorithm splits a data set X = {x_{1} ..., x_{ n }} into k disjoint clusters.
kmodes clustering for SNP data
To incorporate SNP data, the centroid update step of the kmeans algorithm is adapted to calculate centroids from categorical data [20]. Cluster centers are now calculated by counting the frequency of each genotype and using the most frequent genotype (mode) as the new value.
Parallel kmeans/kmodes in shared memory
 (a)
the minimum distance partition (first for loop in function kmeans) and subsequently
 (b)
the centroid update (second for loop).
Instead of explicitly controlling thread concurrency, we here use the concept of transactional memory to indirectly guarantee thread safety (e.g. being lockfree). The number of threads used is influenced by two factors: For calculating the minimum distance partition, the number of data threads equals the number of available CPU cores. Furthermore, each centroid is managed by its own thread. This means that during the assignment step, data is continually sent to the centroids from all data threads, and the centroid update is performed with k threads in parallel.
Transactional memory
In shared memory architectures, there is a need for concurrency control. Simultaneously running threads can process the same data and might also try to change the data in parallel. Opposed to the lowlevel coding via locking and unlocking individually memory registers, transactional memory provides highlevel instructions to simplify writing parallel code [21, 22]. The concept of software transactional memory (STM) that we use here is a modern alternative to the lockbased concurrency control mechanism [23, 24]. It offers a simple alternative to this concurrency mechanism, as it shifts the often complicated part of explicitly guaranteeing correct synchronization to a software system [25]. The basic functionality of software transactional memory is analogous to controlling simultaneous access via transactions in database management systems [26]. Transactions monitor read and write access to shared memory and check whether an action will cause data races. The STM system prevents conflicting data changes by rolling back one of the transactions. Transactions ensure that all actions on the data are atomic, consistent, and isolated. The term atomic means that either all changes of a transaction to the data occur or none of them does. Consistent means that the new data from the transaction is checked for consistency before it is committed. Isolated means that every transaction is encapsulated and cannot see the effects of any other transaction while it is running. As a consequence, transactional references to mutable data via STM enables sharing changing state between threads in a synchronous and coordinated manner.
Cluster number estimation
 1.
Internal criteria: Measure the overlap between cluster structure and information inherent in the data, for example silhouette, intercluster similarity.
 2.
External criteria: Compare different partitions, for example Rand index, Jaccard index, Fowlkes and Mallows.
 3.
Relative criteria: Decide which of two structures is better in some sense, for example quantifying the difference between singlelinkage or completelinkage.
To demonstrate the quality of cluster algorithms, they are often applied to apriori labeled data sets and evaluated by an external criterion [28, 35]. An external index describes to which degree two partitions agree, given a set of N objects X = {x_{1}, ..., x_{ N }} and two different partitions P = {C_{1}, ..., C_{ r }} and Q = {D_{1}, ..., D_{ s }} into r and s clusters respectively.
MCA cluster similarity index
Correction for chance
Cluster validity indices are used to quantify findings about results of a cluster analysis. They do not include information about a threshold for distinguishing between high and low values. Statistical hypothesis testing provides a framework to distinguish between expected and unusual results based on a distribution of the validity index [40, 41]. The null hypothesis is chosen to reflect the case of no inherent cluster structure.
where I_{ max }is the maximum value (which is 1 in case of MCAindex) and E(I) is the expected value under a random hypothesis.
Random label hypothesis
The random label hypothesis simulates the worst case behavior of a clustering. Each data point is randomly assigned to one of the k clusters such that no cluster remains empty, i.e. ∀x_{ i }∈ X assign x_{ i }to cluster C^{ r }, with r uniformly chosen from {1, ..., k} and all C^{ r }≠ ∅. The Monte Carlo simulation for the empirically expected value of the MCA index under this baseline is shown in Figure 4. For the MCA index, the expected value under this hypothesis can also be derived analytically:

If is an integral number, the expected value of matching points between partitions is .

Otherwise, there is at least one cluster expected to have more matching data points, i.e. the expected value is .

E(M CA) is not monotonically decreasing with n, but has a minimum at , see Figure 4.
The number of matching points between partitions cannot decrease when choosing another baseline hypothesis, i.e. this hypothesis reflects the lower bound of the MCA index. Due to the limitations of the Monte Carlo simulation, the expected value of the simulated random label baseline stays constantly above the theoretical limit unless n ≫ k (Figure 4).
Random partition hypothesis
The random partition hypothesis simulates the general behavior of randomly clustering a data set. Under this hypothesis, every partition of n data points into k clusters is assumed to be equally probable. The number of possible partitions is given by the Stirling numbers of the second kind [42]: . Even for small n and k an exhaustive computation of all possible partitions is not feasible. To give an estimate of the expected value under this hypothesis, a Monte Carlo simulation can be used (Figure 4).
Random prototype hypothesis
In contrast to the previous hypotheses, the random prototype hypothesis simulates the average behavior of a clustering with respect to a given data set. k cluster prototypes c_{ j }are chosen randomly, and according to these prototypes, an assignment is performed, e.g. the nearest neighbor rule: ∀ x_{ i }∈ X assign x_{ i }to cluster C^{ r }if r = argmin_{ j }x_{ i } c_{ j }^{2}. Varying the assignment rule enables the simulation of different cluster algorithms (here: nearest centroid for kmeans type clustering). Under this hypothesis, the generated partitions are datadriven and best reflect the random baseline clustering for each data set (Figure 4).
Choosing the appropriate clustering
With a fast cluster number estimation, a two step procedure can be executed to choose the appropriate clustering. The first step consists of choosing a set of k's that have the highest robustness. For this task we and others propose the sensitivity of the clustering as a measure, see the preceding section [32–35, 43–47]. Robustness analysis is based on the observation that for a fixed number of clusters, repeated runs of a cluster algorithm on a resampled dataset often generate different partitions. The robustness of kmeans is also affected by different random initializations. To reduce this effect, kmeans is restarted repeatedly for each resampled dataset. Only the result with minimal quantization error is then included into the list of generated partitions. In this regard, the median value of the MCA index from comparing all generated partitions to another can serve as a predictor for the correct number of clusters. We define the best number of clusters k as the one with maximal distance between median MCA index from cluster results and median MCA index from the random prototype baseline. Statistical hypothesis testing (e.g. MannWhitneytest) can be used to rate the significance of the observed clusterings with respect to the baseline clustering and thus can serve to reject a clustering altogether, meaning no structure in data can be found.
In the second step, we choose the partition with the smallest quantization error for the selected k's. As kmeans does not guarantee to reach a global optimum, but convergence to a local optimum is always given [48], we use the strategy of restarts with different initializations [15]. Finally, the result with the minimal quantization error (least mean squared error) is selected as the best solution. For extremely large data sets, this strategy requires a fast implementation, as several hundreds of repetitions may be necessary [20].
Results
To illustrate the utility of our multicore parallel kmeans algorithm we performed simulations on artificial data, gene expression profiles and SNP data. All simulations of McKmeans were performed on a Dell Precision T7400 with dual quadcore Intel Xeon 3.2 GHz and 32 GB RAM. The four cores on each CPU share 6 MB of cache. Simulations were partly compared to two reference implementations, namely the singlecore kmeans function implemented in R [7] and the networkbased ParaKMeans [6] algorithm. For the kmeans function from R (version 2.9), simulations were also performed on the Dell T7400.
ParaKMeans was tested on the web interface at http://bioanalysis.genomics.mcg.edu/parakmeans. Some of our larger test data could not be processed due to either a slow data loading routine (R) or memory limitations on the master computer. These runtime performance comparisons between different implementations (languages, hardware, software paradigms) can only illustrate a rough difference between single and multicore algorithms and should not be regarded as benchmarks.
Artificial data
Artificial data sets without cluster structure
The influence of changing the number of threads (1, 2, 4, 8, 16) for calculating the minimum distance partition (the number of threads used for the centroid assignment is always k) in McKmeans is shown in Figure 5C. Each box summarizes the results of 10 repeated clusterings for a data set (100000 samples with 500 features). The choice of the number of threads shows best performance if it is in the range of the number of physical CPUs to the number of cores, i.e. 2 to 8 cores.
We also performed a cluster analysis with McKmeans for different numbers of computer cores on a data set (100000 samples with 500 features). A summary of the experiments using 1, 2, 4, and 8 cores is shown in Figure 5D. Using 4 cores resulted in a runtime improvement by a factor of 2 compared to the singlecore experiment. With 8 cores, the CPU usage rate never exceeded 600%, i.e. not all cores were used during calculations.
Artificial data sets with gene cluster structure
We simulated clustered data sets using multivariate normal distributions as the basis for each cluster [49]. An artificial microarray experiment consists of n microarrays being composed of p genes. An experiment is sampled to contain exactly k gene clusters. Withincluster variance and betweencluster variance are used to assemble a set of exactly k wellformed gene clusters as follows: At first, k pairwise equidistant gene cluster centroids μ_{ k }are drawn from an interval around 0 with the variance set to the betweencluster variance . Each gene is assigned to one of the k gene cluster centroids. Then, a genespecific mean μ_{ g }is drawn from a normal distribution with the mean set to the assigned cluster centroid μ_{ k }and variance set to the withincluster variance . The variance of an individual gene over n microarrays follows a χ^{2} distribution with n degrees of freedom. To get an unbiased estimate of the variance, it is divided by n  1, i.e. , with x ~χ^{2}[50]. Only a small fraction of genes in the same cluster is set to have a nonzero correlation. The probability of any genepair to be correlated is set to c = 5 * 10^{(log(p)+2)}. For each cluster the number of correlated genes is determined by a Poisson distribution with mean equal to , where p_{ k }is the number of genes in cluster k. If gene g_{ i }and g_{ j }are correlated, the covariance is calculated from a product of , and the correlation r is drawn randomly from a uniform distribution (r ~U (1, 1)) [6]. The covariance matrix Σ and the gene mean vector μ_{ g }are then used to simulate the different artificial microarrays. An artificial microarray is calculated from Σ and μ_{ g }using the triangular factorization method. A matrix Σ can be factored into a lower triangular matrix T and its transpose T', Σ = TT'. It follows that X = YT + μ_{ g }~N_{ k }(μ_{ g }, Σ), with a matrix Y ~N_{ k }(0, I). The factorization is done with the Cholesky decomposition of Σ [49].
Cluster number estimation on artificial data
To further illustrate the need for a high computational speed of cluster algorithms, we performed simulations to infer the number of clusters inherent in a data set. The stability is measured by comparing the agreement between the different results of running kmeans on subsets of the data. The agreement is measured with the MCA index, and correction for chance is done using the random prototype hypothesis. Here, we simulated the clustered data set using separate multivariate normal distributions as the basis for each cluster. We generated a data set with 100000 cases containing 3 clusters in 100 dimensions. The data set was resampled 10 times leaving out data points. The effect of resampling on the stability of the clustering can be reproduced on this data. The experiment correctly predicts a most stable clustering into 3 clusters. Total running time was 204.27 min. In the simulation 380 separate clusterings were performed. We also performed a cluster number estimation for every artificial data set mentioned in this paper. All simulations predicted the correct number of clusters, see supplementary material (Additional file 1).
Gene expression profiles
Smirnov microarray data
Clustering of gene expression profiles from Smirnov et al. [51].
C ^{1}  C ^{2}  C ^{3}  C ^{4}  

0 hr  67  21  43  24 
2 hrs  68  22  37  28 
6 hrs  62  36  31  26 
Single nucleotide polymorphism data
HapMap SNP data
For evaluating the performance of McKmeans in clustering SNP data, we used the HapMap Phase I SNP dataset [52]. The HapMap project collected SNPs from 270 individuals from four ethnic populations: Yoruba in Ibadan, Nigeria (YRI), CEPH (Utah residents with ancestry from northern and western Europe, CEU), Han Chinese in Beijing, China (CHB), and Japanese in Tokyo, Japan (JPT). For the cluster analysis we only used unrelated individuals. The number of unrelated individuals per group is: 60 YRI, 60 CEU, 45 CHB, and 45 JPT. Only SNPs with a minor allele frequency greater than 0.1 have been included, which resulted in 116678 SNPs.
Clustering of SNP profiles from the HapMap data set. Cluster results for the best clustering with four clusters. Each entry shows the number of individuals that are in Cluster C^{ i }and one of the populations (CHB, JPT, CEU, YRI).
C ^{1}  C ^{2}  C ^{3}  C ^{4}  

CHB  44  1  0  0 
JPT  3  42  0  0 
CEU  0  0  60  0 
YRI  0  0  0  60 
Discussion and Conclusion
Fast algorithms are increasingly becoming important in the individual laboratory, as the sizes of data sets grow and computational demands rise. We have devised a variant of the popular kmeans/kmodes algorithm that effectively utilizes current multicore hardware, so that even complex cluster number estimations for large data sets are possible on a single computer. Computerintensive bioinformatics software is frequently parallelized using a networkbased strategy. Such a parallelization can be very efficient when the same algorithm has to be started several times on different data sets of moderate size, or when different analyses have to be calculated in parallel on the same data set. However, this approach also requires additional effort and equipment, like specialized hardware for fast communication between computers, multiple software installations in heterogeneous environments, or compute cluster administration. For multicore parallelization, OpenMP and functional programming languages provide a basic parallelization scheme through the parallel execution of loops. More efficient parallelization can be achieved through direct use of threads and locking variables, which requires additional effort for concurrency control as well. We have designed a highly efficient parallel kmeans algorithm that utilizes transactional memory, guarantees concurrency, and can serve as a template for other parallel implementations. We achieve a performance increase that scales well with the available resources. An even more dramatic performance gain could be measured in the comparison to the single core kmeans implementation: On 8 cores, the parallel implementation attained a 13fold speed increase (338 min vs 25 min) for a large data set of 1 million cases with 200 dimensions. This disproportionately high increase is partly due to different data loading times of the R implementation and our Java application. For smaller data sets, the highly efficient R implementation, which calls compiled C code, outperforms both our multicore implementation and a networkbased reference implementation on singular cluster runs. Cluster number estimation is often discussed in conjunction with cluster analysis methods, as the number of clusters is an unknown prior [28, 30]. For instance, the gap statistic can be used to search for a strong change in withincluster dispersion across different numbers of clusters [53]. Such approaches that are based on internal cluster measures favor highly compact clusters. Other methods relying on resampling strategies combined with external cluster evaluation measures have been used to additionally incorporate the stability of single clusters [31–33]. Consensus clustering assesses the stability as the percentage of object pairs clustered together [29, 54, 55]. Here, the consensus matrix scales quadratically with the number of objects, and therefore becomes infeasible in clustering extremely large data sets. In contrast, our cluster number estimation method based on resampling and a similarity measure that is linear in the number of objects provides an easy interpretation of the results: Instead of considering pairs of objects, we calculate the percentage of objects clustered together across multiple clusterings. For cluster number estimation across repeated runs of an algorithm, fast implementations become even more important, as simulation time can be extensive even for small data sets. For instance, for a cluster number estimation on a data set consisting of 100 cases and 5000 gene expression values, our multicore algorithm reduces the runtime from 467 min (using the R implementation) to 115 min. For larger data, cluster number estimation now becomes feasible and can give new insights into the data, like suggesting a highly individual radiationinduced response of B cells at the expression level (Smirnov data), or showing that a grouping of individuals is actually possible on the basis of single nucleotide polymorphisms (HapMap data). Our evaluations of the McKmeans algorithm show that it is fast, achieves the same accuracy as the singlecore reference implementations, and is able to cluster extremely large data sets. Furthermore, the Java implementation is easily deployable on different hardware and software platforms. It runs on a single desktop computer and is able to perform complex cluster number estimation experiments due to parallelization.
Availability and requirements
Graphical user interface
The graphical user interface (GUI) software is available for download from our website. Usage of the software is described in the builtin help system. The GUI supports clustering of microarray (real valued) and SNP data. Clustering subjects and clustering genes/SNPs can be done by transposing the imported data set. Gene data is visualized as a scatterplot from two selected dimensions. Furthermore, Sammon's projection method can be performed to show a nonlinear twodimensional projection of the data [56, 57]. Results from the cluster number estimation are given as boxplots. We integrated a statistical test (MannWhitney test) for computing the significance of the best cluster result. The best clustering and the results of the cluster number estimation can be saved for further analysis with statistical software such as R. All plots can be saved as SVG files.
Command line usage
For running batch analyses, McKmeans offers a command line interface to all functions of the GUI version. The command line usage is described on our website.
R package
With the R package "rMcKmeans", the multicore kmeans algorithm is fully integrated into the R software framework. rMcKmeans is based on the Java implementation and is freed from three important limitations in R: (a) R can only process data sets with up to 2 billion entries, while Java supports datasets of size 2^{31} × 2^{31}, (b) loading time of extremely large datasets in R is extensive, and (c) R does not yet support true multicore programs. All available multicore packages in R cannot share memory and internally have to replicate the data for every used core, resulting in a lower amount of total memory available for computing.
McKmeans is a Java program implemented in Clojure (freely available at http://www.clojure.org). McKmeans can also be called from R (package rMcKmeans).

Project name: McKmeans

Project home page: http://www.informatik.uniulm.de/ni/mitarbeiter/HKestler/parallelkmeans

Operating system(s): Platform independent

Programming language: Java, R

Other requirements: Java 1.6 or higher

License: Artistic License 2.0

Any restrictions to use by nonacademics: no
Declarations
Acknowledgements
We thank Christoph Müssel for R support. This work is supported by the German Science Foundation (SFB 518, Project C5), the Stifterverband für die Deutsche Wissenschaft (HAK), and the Graduate School of Mathematical Analysis of Evolution, Information, and Complexity at the University of Ulm (HAK, JMK).
Authors’ Affiliations
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