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# Statistical Applications in Genetics and Molecular Biology

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Volume 15, Issue 2

# A graph theoretical approach to data fusion

Justina Žurauskienė
• Theoretical Systems Biology Group, Centre for Bioinformatics, Imperial College London, South Kensington Campus, SW7 2AZ, London, UK
• Other articles by this author:
/ Paul D.W. Kirk
/ Michael P.H. Stumpf
• Corresponding author
• Theoretical Systems Biology Group, Centre for Bioinformatics, Imperial College London, South Kensington Campus, SW7 2AZ, London, UK
• Email
• Other articles by this author:
Published Online: 2016-03-18 | DOI: https://doi.org/10.1515/sagmb-2016-0016

## Abstract

The rapid development of high throughput experimental techniques has resulted in a growing diversity of genomic datasets being produced and requiring analysis. Therefore, it is increasingly being recognized that we can gain deeper understanding about underlying biology by combining the insights obtained from multiple, diverse datasets. Thus we propose a novel scalable computational approach to unsupervised data fusion. Our technique exploits network representations of the data to identify similarities among the datasets. We may work within the Bayesian formalism, using Bayesian nonparametric approaches to model each dataset; or (for fast, approximate, and massive scale data fusion) can naturally switch to more heuristic modeling techniques. An advantage of the proposed approach is that each dataset can initially be modeled independently (in parallel), before applying a fast post-processing step to perform data integration. This allows us to incorporate new experimental data in an online fashion, without having to rerun all of the analysis. We first demonstrate the applicability of our tool on artificial data, and then on examples from the literature, which include yeast cell cycle, breast cancer and sporadic inclusion body myositis datasets.

This article offers supplementary material which is provided at the end of the article.

## 1 Introduction

Given the broad variety of high-throughput biological datasets now being generated, attention is increasingly focusing on methods for their integration (Kirk et al., 2012; Lock and Dunson, 2013; Wang et al., 2014). Different technologies allow us to probe different aspects of biological systems, and combining these complementary perspectives can yield greater insight (Altman, 2013; Savage et al., 2013; Schimek et al., 2015).

Computational techniques for data fusion are rapidly evolving, and moving towards potential clinical applications (Altman, 2013). For example, recently proposed methods try to identify cancer subtypes using fused similarity networks applied to a combination of DNA methylation, mRNA expression and miRNA expression datasets (Wang et al., 2014). Cancer subtype discovery has also been a focus of other recent data integration efforts (Yuan et al., 2011; Savage et al., 2013; Lock and Dunson, 2013). Further, data exploration via e.g. simultaneous clustering of gene expression networks (Narayanan et al., 2010), inference of transcriptional module networks (Lemmens et al., 2009), and bi-clustering with connected biologically relevant information (Reiss et al., 2006) are also becoming prominent in the recent data fusion literature.

Data integration methods can be categorized as either unsupervised (the subject of the present work), or supervised (Troyanskaya et al., 2003; Myers et al., 2005; Myers and Troyanskaya, 2007; Huttenhower et al., 2009). Existing unsupervised techniques for the fusion of multiple (i.e. more than two) datasets fall into one of two broad categories: those which are Bayesian (Kirk et al., 2012; Lock and Dunson, 2013) and those which are not (Shen et al., 2009; Wang et al., 2014). For many real-world or large-scale analyses the lack of suitable training sets places severe limitations on supervised algorithms, and unsupervised learning methods have thus gained in popularity. Current Bayesian approaches for unsupervised data fusion rely on mixture model representations of each dataset, with dependencies between datasets modeled either using coefficients that describe the similarity between pairs of datasets (Kirk et al., 2012), or by assuming that each dataset has a structure that adheres – to a lesser or greater degree – to an overall consensus structure that is common to all datasets (Lock and Dunson, 2013). Bayesian approaches have the advantage of having firm probabilistic foundations, of forcing all prior beliefs and assumptions to be formally expressed from the outset, and of allowing the uncertainty in unknown quantities to be encapsulated in (samples from) posterior densities. For these reasons, Bayesian approaches are usually preferred; however, computational cost may prohibit their application to large (e.g. genome-scale) datasets.

In this work we introduce a new approach for the fusion of heterogeneous datasets; the methodology presented here is closely related to a graph-theoretic approach, which may be used to test for associations between disparate sources of data (Balasubramanian et al., 2004). Our approach has two basic steps. In the first, we obtain (independently) for each dataset either an ensemble of networks (in the Bayesian case), or a single network (in the non-Bayesian case), where networks are used to represent the structure and dependencies present in the dataset. In the second, we perform a post-processing step which compares the networks obtained for different datasets, in order to identify common edges, and to thereby assess and quantify the similarities in dataset structure.

Although, in principle, we could consider any type of structure that may be represented by a network, in the present work we are specifically interested in identifying and comparing the clustering structure possessed by each dataset, and it is at this level that we perform data fusion (Figure 1). In the Bayesian case, we employ for the purpose of cluster identification Dirichlet process mixture (DPM) models with either Gaussian process (GP) or multinomial likelihood functions. In our approach, data fusion is performed by constructing the connectivity networks that represent each clustering, and then forming “consensus networks” that identify the clusters upon which multiple datasets agree.

Figure 1:

Method illustration. It is common to visualize the clustering outcome in a “table-like” fashion, by listing all genes next to their associated cluster labels. To visualize this, we construct corresponding graphs; here, each node in the network represents a gene and a line indicates that two genes cluster together. We use different color schemes to represent cluster labels. By adopting a graph-theoretical approach we can represent each network as an adjacency matrix, which in turn can be used for data integration. (A) Illustrates an artificial example of 12 genes that are assigned into three clusters (e.g. control case) from the first dataset. (B) Illustrates the same list of genes assigned into different three clusters (e.g. disease case) from a second dataset. (C) Illustrates the corresponding network (and cluster assignment) after performing data integration step.

The integration step is somewhat similar to the consensus clustering approach (Monti et al., 2003), which was developed for the purpose of assessing cluster stability and for identifying the consensus across multiple evaluations of the same clustering approach. In contrast with other existing techniques (Kirk et al., 2012; Lock and Dunson, 2013), in our approach each dataset is initially considered independently. Although this is likely to result in some loss of sensitivity, it also means that computations can be performed in a parallel fashion, which offers potentially significant advantages in cases where we are dealing with large datasets, or where it is necessary to rerun computations in order to consider additional datasets.

## 2 Methods

Here we develop a novel graph theoretical approach for integrating clustering outcomes across several datasets, which we refer to as “GTA” for brevity. GTA may be applied to the output of Bayesian or non-Bayesian clustering algorithms.

## 2.1 Data integration

There are many different methods for data integration, most of which set out to accomplish one (or both) of the following two key aims: (i) modeling the dependencies that exist within and between datasets; and (ii) combining the predictions derived from one dataset with those derived from another. Assuming for convenience of notation that we wish to integrate just a pair of datasets, we might consider that the “ideal” way to fulfill the first of these two aims would be to model the joint distribution, p(q(1), q(2)|D(1), D(2)), of the predictions, q(1) and q(2), derived from datasets, D(1) and D(2), respectively (for the sake of generality, we leave the definition of q deliberately vague, but these predictions could be, for example, assessments of disease risk). Such an approach poses many potential challenges, not least that the datasets may be of very different types and/or may be of (very) high dimension. In contrast, the second aim just requires us to define a fusion function, f, for combining the predictions. We shall assume that this function is deterministic; i.e. for given predictions, q(1) and q(2), we assume that f maps the predictions onto a single combined output, f(q(1), q(2)). One challenge in this case is to assess the uncertainty/confidence in this output. If we were able to sample M pairs, $(q1(1), q1(2) ), (q2(1), q2(2) ), …, (qM(1), qM(2) )$ from the joint distribution, p(q(1), q(2)|D(1), D(2)), then we could consider the set ${f(qm(1), qm(2) )}m=1M$ in order to assess the variability in the output.

In general, modeling the joint distribution, p(q(1), q(2)|D(1), D(2)), is much more computationally demanding than defining a fusion function. To make modeling p(q(1), q(2)|D(1), D(2)) more tractable, here we make an independence assumption and factorize the joint distribution as,

$p(q(1), q(2) |D(1), D(2) )≈p(q(1) |D(1) )p(q(2) |D(2) ). (1)$(1)

While, in practice, the quality of this approximation will depend upon a number of factors (including the signal-to-noise ratio associated with the individual datasets), it has the advantage of circumventing many of the challenges associated with trying to model p(q(1), q(2)|D(1), D(2)). Moreover, this independence assumption means that we may perform computations for each dataset in parallel, allowing us to scale to potentially large number of datasets. Having made this independence assumption, we may obtain samples from the joint distribution by sampling independently from each of the factors, p(q(1)|D(1)) and p(q(2)|D(2)). For a given fusion function, f, we may then consider the set ${f(qm(1), qm(2) )}m=1M,$ as described above. Extending to R datasets is straightforward: we simply obtain samples independently from each p(q(r)|D(r)) for r=1, …, R, and then consider the set ${f(qm(1), qm(2), …, qm(R))}m=1M.$

## 2.2 GTA: a graph theoretic approach to unsupervised data integration

We start with a collection of datasets, D(1), …, D(R), each of which comprises measurements taken on a common set of N entities/items (e.g. genes or patients). We consider the situation in which the prediction, q(r), associated with dataset D(r) is the clustering structure possessed by these items. To proceed, we must therefore define: (i) a method for sampling from p(q(r)|D(r)); and (ii) a fusion function, f, for combining the predicted clustering structures derived from the various datasets. Here, our aim is to identify similarities between the clustering structures associated with each of the datasets.

## 2.2.1 Sampling from p(q(r)|D(r))

We consider two different approaches for sampling from p(q(r)|D(r)). Where possible, we use Dirichlet process mixture modeling, a nonparametric Bayesian approach, which is discussed in the Appendix A. However, in some cases the size of the datasets being considered prohibits the use of such approaches. In these instances, rather than using an ensemble of M samples from p(q(r)|D(r)), we instead take M=1 and treat the maximum likelihood estimate, $qML(r),$ as a single, representative sample.

## 2.2.2 Defining the fusion function

In order to define a fusion function, f, we take inspiration from Balasubramanian et al. (2004) work and adopt a graph theoretic approach. We define c to be a clustering of the N items of interest (genes, patients, etc.), so that ci is the cluster label associated with item i. The N×N adjacency matrix is given as,

$(A)ij={1,if ci=cj;0,otherwise.$

Given a collection of R such clusterings, say c(1), …, c(R), we may form a corresponding collection of adjacency matrices, A(1), …, A(R), where A(k) is the adjacency matrix representation of clustering c(k). The Hadamard (entry-wise) product of these matrices, H=A(1) ∘…∘A(R), defines a new clustering, in which items i and j appear in the same cluster if and only if all of the clusterings c(1), …, c(R) agree that they should appear in the same cluster. From a graph theoretic perspective, H corresponds to the graph formed by taking the intersection of the graphs defined by A(1), …, A(R) (see Figure 1). Assuming that each of the clusterings, c(1), …, c(R), corresponds to a different dataset, we define our fusion function f to act on these and then return the clustering corresponding to the Hadamard product, H. Equipped with this fusion function, and M samples from p(q(r)|D(r)) (for r=1, …, R), we may proceed to describe with the GTA algorithm (Algorithm 1).

Algorithm 1:

The GTA algorithm.

## 2.2.3 Summarizing the fused output

The output of the GTA algorithm is a collection of M fused clusterings. While these provide a useful indication of the uncertainty in the fused output, it is often also helpful to condense these into a single, summary fused clustering, c̅. This can be done by constructing a posterior similarity matrix (Fritsch and Ickstadt, 2009) of $c^1, …, c^p$ and maximizing the posterior expected adjusted Rand index (Hubert and Arabie, 1985).

## 2.2.4 Heuristic score of clustering similarity

In some instances, it is useful to measure the compatibility between data sources by comparing the independent clusterings (obtained before data integration) with the fused clustering (obtained using the GTA algorithm). Due to the nature of our technique it is expected to observe more clusters after the data integration process. This is particularly true when studying less related datasets and when integrating more than a few data sources. We therefore define the following measure of similarity between any two data sources Dr and DI,

$S(Dr, Dl)=(KDr+KDl)/2KDr∘Dl, (2)$(2)

where $KDr$ and $KDl$ correspond to the number of clusters before data integration, and $KDr∘Dl,$ the number of clusters after integration. Here, the score S can have any value between zero and one. The closer S is to 0, the more dissimilar datasets are. On the other hand, the closer S is to 1, the more substantial the similarity between the structure of the two datasets.

## 3 GTA applications

In this section we explore the capabilities of GTA to data integration. Here we are interested in comparing our result to the result delivered by data fusion methods, which explicitly model relationships and dependencies between datasets. We start by illustrating the applicability of heuristic score to identify similarities between several data sources. Then we test GTA performance on popular examples from literature, and on sporadic inclusion body myositis dataset.

## 3.1 Capturing similarities across artificial dataset

We consider a S. cerevisiae dataset (Cho et al., 1998) that contains mRNA transcription levels taken to study the cell cycle. From 416 genes that had previously been identified to have periodic changes in transcript levels we select 100, and assign them into seven clusters using DPM with GPR likelihood model (Figure 2A). The details regarding MCMC specification and diagnostics are summarized in Appendix B. To demonstrate the performance of GTA, we further consider the artificial dataset example (Kirk et al., 2012) that was constructed using the same 100 genes. Briefly, this example consists of six data sources, where the first source is the original dataset (see Figure 2A), and the other five were obtained sequentially, by randomly permuting a quarter of gene names in the previous dataset. Applying GTA on pairwise combinations of these datasets we identify the numbers of genes that cluster together before and after the fusion. These can be used for computing the score of agreement and for determining the similarities across all six datasets. The pairwise similarities are summarized in Figure 2B where columns and rows identify which combination of datasets were considered, and color illustrates the level of similarity. Alternatively, the similarity between these datasets can be identified from the final clusterings by computing the adjusted Rand index (ARI) (Hubert and Arabie, 1985). The ARI compares two given partitions of the same list of genes and is based on how often a gene (observation) is associated with the same cluster in both partitions (see Figure 2C).

Figure 2:

GTA applications to six artificial datasets. (A) Illustrates genes from Cho et al. (1998) sorted into seven clusters using DPM model with GP likelihood. (B) Illustrates similarity between six final clusterings using similarity measure S(Dr, Dl) outlined in (2). (C) Illustrates similarity between the same clusterings using adjusted Rand index. (D) Illustrates the effects of Hadamard product – each heatmap corresponds to the adjacency matrix constructed from original dataset, D1, and the first modified dataset, D2.

## 3.2 Integrating cell cycle datasets

We next compare the results from GTA to the results by Multiple Dataset Integration (MDI) (Kirk et al., 2012). In this example we consider integrating a number of datasets from yeast cell cycle studies. The first dataset contains gene expression time courses (Granovskaia et al., 2010), where mRNA measurements are taken at 41 time points across 551 genes that exhibit oscillatory expression profiles. The second dataset is ChIP-chip data (Harbison et al., 2004) that contains binary information about proteins binding to DNA, and the third is a protein-protein interaction (PPI) dataset from BioGRID (Stark et al., 2006).

In order to apply GTA for data fusion, we initially cluster all datasets by running in parallel three independent DPM models (see Appendices A and B). To specify the DPM, we use Gaussian process likelihood to cluster gene expression time courses, and multinomial likelihood to cluster the transcription factor binding and PPI datasets. As before, further details regarding MCMC specifications and diagnostic plots are summarized in Appendix B. Although we use DPM here to automatically determine the number of cluster for each dataset; it is worth noting that initial clustering could also be done using other methods since GTA operates on pre-clustered dataset.

In this example we are aiming to compare the results from our method to the results from MDI, for this reason we consider two cases: (i) integration of gene expression and transcription factor binding data; (ii) integration of gene expression, transcription factor binding, and protein-protein interaction data.

MDI is a tool that jointly clusters all datasets by modeling dependencies between them. Using MDI approach the final clustering can be extracted by calculating a fusion probability – the probability that any two genes are fused in two datasets, and by removing those genes where this probability is less than 0.5. For this reason, using GTA we can also consider removing genes that lack the evidence of clustering together. This can be achieved by computing the matrix $P=1M∑m=1MHm,$ where each matrix entry is probability, Pij, for gene i and gene j to be in the same cluster in both gene expression and transcription factor binding datasets; and removing genes i, where Pij<0.5 for every j. The above procedure is somewhat analogous to MDI in terms of looking only at those genes that are fused across both datasets. Then, applying the approach of Fritsch and Ickstadt (2009) to filtered posterior clusterings we obtain the final data partition that assigns genes into clusters based on information from both datasets. Figure 3A,C illustrates the performance of GTA, where genes are allocated into clusters based not only of their expression profiles but also on which transcription factors bind to DNA. In order to compare our results to the results obtained by MDI we use overlap score (OS) metrics (Nepusz et al., 2012; Zhang et al., 2015), OS(A, B)=|AB|2/|A||B|, where |·| denotes the number of elements in the set; A is predicted network/clustering structure by GTA, and B is a benchmark structure, in this example it is obtained using MDI. A predicted clustering can be considered as a match to the benchmark clustering if their OS value is no less than a predefined threshold, which typically can be set to 0.2 (Bader and Hogue, 2003; Wu et al., 2009; Zhang et al., 2015). In this example we obtained OS=0.426, which indicates that GTA can provide the approximation to MDI result. In order to better understand the difference between both clusterings we looked at corresponding network structures (Figure 3A,B). In this case MDI maintains densely connected clusters, whereas the GTA output is dominated by small clusters. Although GTA is less sensitive in detecting larger clustering structures, it took less than a minute for algorithm to fuse M=1000 samples from posterior (running time=40.665 s, was obtained using R function proc.time()); it was reported (Kirk et al., 2012) that it took approximately 2 hours to execute MDI on the same example using bag-of-words model, and approximately 4 hours to run it using multinomial model. This suggest that GTA can be seen as a useful approximation to MDI, which offers considerable savings on computational times.

Figure 3:

GTA applications to yeast cell cycle datasets. Integrating yeast cell cycle time course and transcription factor (TF) binding datasets. Here a line indicates that any two genes are assigned to the same cluster after the fusion ((A)/(B)). (A) Networks illustrates final clustering structure using fused samples from GTA. (B) Networks illustrates final clustering structure using MDI. (C) Further illustrate three additional clusters identified by GTA; on the left – gene expression time courses are projected on a heatmap of TF binding data on the right, here yellow color indicated that a TF is binding to a gene. Horizontal black lines mark cluster boundaries.

As a second step in our yeast cell cycle example we consider integrating three datasets: gene expression, transcription factor binding and protein-protein interaction (PPI) data. In order to also fuse the PPI dataset using MDI, it is necessary to rerun joint clustering from the beginning; however, using GTA we can benefit from previously pre-clustered data and perform data fusion in an “online-fashion” using only samples from the posterior. In this case GTA fuses three datasets in under a minute (40.889 s), whereas for MDI it took to generate approximately 90 samples per chain per hour Kirk et al. (2012). Applying thinning-out strategy (removing genes that lack the evidence of clustering together) we obtained a set of 14 genes that can be assigned into 6 clusters (for comparison MDI assigned 16 genes into 5 clusters). Supplementary Figures 3A,B show the final network structures that correspond to fused three datasets using GTA and MDI, respectively; in addition, Supplementary Figure 2 projects clusters from GE data on to TF and PPI. For convenience, Supplementary Material Tables 3 contains further details regarding gene function. In addition to this, we looked at the overlap score, OS=0.214, which is above predefined threshold and suggests that GTA results can be seen as a useful approximation.

## 3.3 Breast cancer data

In this example we explore the performance of our data integration technique on a breast cancer dataset, where we aim to integrate four different data sources taken from The Cancer Genome Atlas (Cancer Genome Atlas Network, 2012). We use a previously described dataset (Lock and Dunson, 2013) that consists of preselected 348 tumor samples characterized in four different ways: RNA gene expression (645 genes), DNA methylation (574 probes), miRNA expression (423 miRNAs), and reverse phase protein array (171 proteins). In order to cluster all data sources, we adopt a modified version of Bayesian consensus clustering (BCC) approach Lock and Dunson (2013). BCC is a data integration technique that seeks to simultaneously model data specific and shared features by inferring the overall clustering Ĉ (that describes all datasets), and by inferring data specific clusterings $L^i, i=1, …, 4.$ The source specific clustering is controlled by parameter α=[α1, …, α4], which express the probability of how much each Li contributes to the overall Ĉ. Our goal is to pre-cluster each dataset without inferring the overall clustering Ĉ and then use GTA to fuse all four datasets. For this reason we fix the probability α=1 and cluster each dataset independently using publicly available R code (Lock and Dunson, 2013). Next, applying GTA with M=1000 on posterior samples we can identify the fused clustering c̅. To run GTA on pre-clustered data takes under a minute (running time was 40 s on a MacBook Pro), however to run a full joint clustering using BCC took about half an hour. In order to compare both clusterings we looked at the overlap scores (see Table 1), which indicate that GTA result can be considered as a fast approximation to the BCC fused clustering.

Table 1:

Overlap scores between GTA clusters and corresponding BCC clusters.

Breast cancer is a heterogeneous disease, for this reason four biologically distinct molecular subtypes can be connected to these dataset (Cancer Genome Atlas Network, 2012; Lock and Dunson, 2013). They are known as Her2, Basal, Luminal A, Luminal B, and are associated with different clinical prognosis (Rakha et al., 2008; Dawood et al., 2011). In order to further assess our results we look at cancer subtypes that are associated with each cluster and compared these to the BCC clusters. Confusion matrices in Table 2 illustrates the summarized results. The first matrix corresponds to the outcome using BCC method (a single run of publicly available code), while the second matrix summarize results from GTA. This further demonstrates that clusters identified using our technique bear similarity to the BCC results.

Table 2:

Comparison between BCC overall and GTA final clusterings.

## 3.4 Sporadic inclusion body myositis

In this section we apply our technique on clinical gene expression datasets that include: (i) sporadic Inclusion Body Myositis (sIBM), which is an inflammatory muscle disease that progresses very slowly, causes muscular weakness and eventually muscle atrophy (Grau and Selva-O’Callaghan, 2008; Machado et al., 2009); (ii) polymyositis (PM) which causes chronic inflammation of the muscles; and (iii) a dataset containing human protein-protein interactions (BPPI) (see Supplementary Material, Section B for further details). Both sIBM and PM are associated with aging but interestingly sIBM can be frequently misdiagnosed as PM, and the explicit diagnosis can only be confirmed via a muscle biopsy (Dalakas, 2006). Current understanding is that sIBM is driven by two coexisting processes (autoimmune and degenerative); however, the actions by which sIBM occurs are still only poorly understood (Dalakas, 2006; Needham and Mastaglia, 2007).

## 3.4.1 PM and sIBM data integration

Here we focus on experimental sIBM and PM datasets that have 5 and 3 data points (clinical cases). In order to apply our technique, we select 424 genes that where previously identified to have the largest variation in their expression across all data points (Thorne et al., 2013). In order to cluster these datasets, we employ “mclust” package in R, which fits a Gaussian mixture model and uses the Bayesian information criterion to estimate the number of components. Because we do not have access to the clustering samples from the posterior for each dataset, we use GTA with a special case M=1 to integrate single clusterings from both datasets. The integrative analysis enables partitioning of large PM and sIBM clusters into smaller ones; however, this results in a greater number of clusters after the fusion, see Figure 4. To validate our results we use the “ToppGene” (https://toppgene.cchmc.org) tool, which performs gene set enrichment analysis and allows the detection of functional enrichment for phenotype (disease) and GO terms such as biological function. Such analysis enabled us to identify those clusters (5 out of 12) that are enriched with diseases like rheumatoid arthritis and myositis, and biological processes related to response from immune system. This suggests that genes in disease enriched clusters might play an important and shared role in both PM and sIBM, and for this reason they are promising targets for further analysis.

Figure 4:

GTA applications to myositis datasets. Illustrate clusters obtained by integrating PM and sIBM gene expression datasets using GTA. Each network represents a fused cluster, which is associated with one of enriched ontologies, biological process (BP), and disease (D).

## 4 Discussion

In this paper we have developed and illustrated an alternative way to integrate data generated from different sources. GTA mainly relies on the outcomes from Bayesian clustering approaches and is based on concepts from graph theory. We have demonstrated that our technique, can produce similar data fusion results when compared to recently proposed data integration methods. Equally, while GTA can fuse the outcomes from Bayesian clustering algorithms, the special case M=1 can be applied in order to fuse a single clusterings across various datasets.

Here we have demonstrated the applicability of our technique to a variety of typical biological and biomedical problems: the identification of potentially underlying regulatory mechanisms in the yeast cell cycle; sub-typing tumors in breast cancer data; and exploring similarity patterns across inflammatory muscle diseases. We have compared our technique to MDI and BCC, the current state-of-the-art techniques used to address similar data integration problems. The main benefits of our graph-theoretical approach include: (i) the applicability to Bayesian and non-Bayesian type clustering approaches. This means that our methodology can be applied in order to model multiple sources on a genome scale data without facing computational challenges; and (ii) ability to perform clustering in a parallel fashion. These features might be advantageous in situations where it is necessary to rerun computations in order to consider additional datasets. As part of our modeling approach, we have defined a measure of similarity between two data sources. This can be used to evaluate the effects of data integration routine and in order to assess the agreement between data sources.

We note that it is possible to apply our graph-theoretical approach to the outcomes from simple clustering techniques, for example hierarchical or K-means clustering. This could be done by first performing a bootstrapping approach on each gene within a dataset Dr, M times; for further details on bootstrapping see (Efron, 1981) and (Kerr and Churchill, 2001). This would produce a set of bootstrapped datasets $Drb1, …, DrbM.$ The bootstrapped datasets together with the initial dataset can be clustered using a standard hierarchical clustering algorithm. The clustering outcomes can to some extent be viewed as being the analogs to the samples from posterior. Then after bootstrapping all data sources we can use GTA to perform integrative modeling. This process can be seen as a frequentist modeling approach to data integration.

## Acknowledgments

This work was supported by the Leverhulme Trust (to JŽ and MPHS), the Royal Society (to MPHS), HFSP (to PK and MPHS) and BBSRC (to MPHS).

## A.1 Dirichlet process mixtures

The methodology for modeling heterogeneity in genomic datasets bears similarity to the structure of an infinite Gaussian mixture model. A Dirichlet process mixture (DPM) model can be derived as a limit of a finite mixture model when the number of mixture components grows to infinity. Precisely, let consider a dataset D={x1, …, xN} that we intend to model by the following mixture model,

$p(x1, …, xN|π, θ)∼∑k=1Kπkℱ(D|θk), πk>0, ∑k=1Kπk=1, (3)$(3)

where K is the number of components, πk are the mixing proportions, and ℱ (D|θk) are component density functions parameterised with a set of parameters θk. Furthermore, we associate each data point, xi, with a component indicator variable ci∈{1, …, K}. This allow us to track which mixture component generated a data point xi. We can allocate a symmetric Dirichlet prior to the mixing proportions, $p(π1, …, πK|α)=Γ(α)/Γ(α/K)K∏k=1Kπkα/K−1,$ where α is a concentration parameter; and a multinomial prior, $p(c1, …, cK|π)=∏k=1Kπknk,$ to the indicator variables with nk indicating the number of times ci=k (the number of observations that have same indicator value). Then a conditional prior for a single indicator, all others being given, is obtained by integrating over the mixing proportions

$p(ci=k|c−i, α)=n−i,k+α/KN−1+α,$

where the subscript, “–i,” is a short notation for all indicators excluding i; and ni,k denotes the number of observations within the cluster k not including observation xi. Now, by taking the limit as K goes to infinity the conditional prior has the following limits,

$p(ci=k|c−i, α)=n−i,kN−1+α, (4a)$(4a)

$p(ci≠ci′, i′≠i|c−i, α)=αN−1+α. (4b)$(4b)

Combining conditional priors (4) with a likelihood function, ℱ(xi|θk), will result in a conditional posteriors

$p(ci=k|c−i, α)∝n−i,kN−1+αℱ(xi|θk), (5a)$(5a)

$p(ci≠ci′, i′≠i|c−i, α)∝αN−1+α∫ℱ(xi|θj)H(θj)dθj, (5b)$(5b)

that are necessary to perform the inference of all parameters associated with model (3), including the number of clusters K. This can be achieved via Markov chain Monte Carlo (MCMC) methods. In equations (5), H denotes a prior for parameters θk, which might be a conjugate prior and depends on the likelihood model.

The DPM model is a general framework, and here we will focus on specific likelihood models. Specifically, we will employ DPM of Gaussian process regression (GPR) models to cluster gene expression time series, and DPM of multinomial models to model categorical/discrete functional genomics data. These two likelihood options are incorporated in our Matlab package DPMSysBio.

## A.2 Likelihood function for the time course data

For convenience, bellow we will use the following notation, xixi. Instead of specifying a parametric (e.g. a multivariate-Gaussian) likelihood function, in this work we capture the time course observations xi ={xi(t1), …, xi(tp)}, where xi(tj) denotes the measurement taken on gene i at time point tj, with a regression model. In a regression approach, each gene xi can be expressed as

$xi(tj)=fi(tj)+εij,$

where fi is a regression function and εij~𝒩(0, σ2) is added to express the potential uncertainty in measurements. In our case we are modeling observations (genes) that tend to cluster together. This means that each cluster can be described by the same “data generating” function fifk and noise $σi2≡σk2$ model; here, k=1, …, K. In order to identify function fk=[fk(t1), …, fk(tp)] for each cluster, we adopt a Bayesian nonparametric approach by specifying a Gaussian process prior for the function fk. Formally, a Gaussian process is a collection of random variables, any finite number of which have a joint Gaussian distribution Rasmussen and Williams (2006). In order to specify a GP prior we need to define two main characteristics – a mean, m, and covariance, cov, functions. Such GP prior allow us to describe the Gaussian distributions that are associated with unique gene clusters. In simple terms this means that the function fk evaluated at a finite number of input points t1, …, tp will have a multivariate Gaussian distribution with zero mean and there exists a covariance function, cov, such that,

$[fk(t1), …, fk(tp)]T∼𝒩(0, cov(ti, tj)); ti, tj−are any two inputs.$

Here, for simplicity, we adopted a zero mean function (m(t)=0, for all t) and squared exponential function,

$cov(ti, tj)=ak2exp(−(ti−tj)22lk), (6)$(6)

where ak, lk>0 are the hyper-parameters. Then, the genes (observations) within each cluster, k,

$x1(k), …, xNk(k)|fk, σk2∼𝒩(fk, σk2Ip).$

Here, Nk is the number of observations in cluster k. For convenience we can rewrite the above in an expanded form,

$[x1(k)(t1), …, xNk(k)(t1), …, x1(k)(tp), …, xNk(k)(tp)]|fk, σk2∼𝒩([fk(t1), …, fk(t1), …, fk(tp), …, fk(tp)], σk2INkp),$

where [fs(t1), …, fk(t1), …, fk(tp), …, fk(tp)]T contains Nk replicates of each fk(tj).

Now, we can define a Gaussian process prior,

$[fk(t1), …, fk(t1), …, fk(tp), …, fk(tp)]T|ak, lk∼𝒩(0, cov(k)).$

Here cov(k) is an Nkp×Nkp matrix that is composed of smaller block matrices,

$([cov(t1, t1)]⋯[cov(t1, tp)]⋮⋱⋮[cov(tp, t1)]⋯[cov(tp, tp)]),$

where [cov(ti, tj)] denotes i, j-th a smaller matrix structure. Here, each block matrix is symmetric and positive definite. This enable us to specify the following likelihood function within each cluster k,

$[x1(k)(t1), …, xNk(k)(t1), …, x1(k)(tp), …, xNk(k)(tp)]|ak, lk, σk∼𝒩(0, cov(k)+σk2INkp) (7)$(7)

## A.3 Likelihood function for the discretised data

For convenience in this section we will describe a multinomial model Kirk et al. (2012) to capture categorical data. Typically, the categorical dataset consist of a list of genes (objects) where measurements, r∈{1, …, R}, for each gene are taken at Q distinctive attributes. For genes that tend to cluster together, xrq denotes the number of times q-th attribute receives a value r. Thus, the multivariate probability mass function for categorical data,

$p(xq|θ1q, …, θRq)∝∏r=1Rθrqxrq, ∑r=1Rθrq=1,$

where xq=[x1q, …, xRq]; and θrq denotes the cluster related probability for attribute q to receive a value r.

Setting a Dirichlet prior, $𝒟(β1q, …, βRq),$ for θ1q, …, θRq, we obtain

$p(xq|β1q, …, βRq)=Γ(Bq)Γ(Sq+Bq)∏r=1RΓ(xrq+βrq)Γ(βrq),$

where Bq=β1q, …, βRq and Sq=x1q, …, xRq. From the independence between the attributes follows the marginal likelihood function,

$f(x1, …, xQ|β)=∏q=1QΓ(Bq)Γ(Sq+Bq)∏r=1RΓ(xrq+βrq)Γ(βrq),$

where βR×Q is a matrix.

## B Inference of the hyper–parameters

In this section we explain how inference is performed for DPM models. Additionally, we provide the Markov chain Monte Carlo (MCMC) run details for S. cerevisiae and yeast cell cycle (examples in the paper).

In the DPMSysBio package, the Gaussian process likelihood is controlled by three hyper-parameters, θc={ac, lc, σc}, that are necessary in order to learn the means and covariances of each cluster. We set a Gaussian priors for the logarithmic versions of hyper-parameters (log(θc)) and employ a Gibbs sampling algorithm as described in Neal (2000) (see Section 6 for details). This algorithm can be seen as the most general Gibbs sampling scheme that can deal with a non-conjugate priors. In order to learn the hyper-parameters of DPM model with multinomial likelihood, we use Dirichlet priors.

Finally, to infer the concentration parameter α we set the following gamma prior α~𝒢(2, 4), and adopt approach Escobar and West (1995) proposed by Escobar and West.

## B.1 S. cerevisiae example

For the original time courses Cho et al. (1998) and five perturbed datasets, we ran DPMSysBio package with GPR likelihood for 50,000 iterations recording each 5th sample. This provided us with 10,000 “thinned-out” MCMC samples. Further, we discarded the first 5000 samples as a “burn-in” period and for further analysis we used 5000 samples per each dataset.

## B.2 Yeast cell cycle datasets example

• For time course dataset (Granovskaia), we ran DPMSysBio package with GP likelihood for 40,000 iterations recording each 5th sample. This provided us with 8000 “thinned-out” MCMC samples. Further, we discarded the first 5000 samples as a “burn-in” period and for further analysis we used 3000 samples.

• For transcription factor binding dataset (Harbison), we ran DPMSysBio package with multinomial likelihood for 20,000 iterations recording each 5th sample. This provided us with 4000 “thinned-out” MCMC samples. Further, we discarded the first 2000 samples as a “burn-in” period and for further analysis we used 2000 samples.

• For protein-protein interaction dataset (Biogrid), we ran DPMSysBio package with multinomial likelihood for 30,000 iterations recording each 5th sample. This provided us with 6000 “thinned-out” MCMC samples. Further, we discarded the first 3000 samples as a “burn-in” period and for further analysis we used 3000 samples.

Figure 5 illustrates the Markov chains and posterior distributions for the number of clusters, K, and the concentration parameter, α, for Granovskaia (TC), Harbison (TF) and Biogrid (PPI) datasets.

Figure 5:

MCMC diagnostics plots. In the first column figures illustrate a “thinned-out” Markov chains for the concentration parameter, α; in the second column are given posterior distributions for α; in the third column – a “thinned-out” Markov chains for the number of clusters, K; in the fourth – posterior distributions for K. (A) Time course datasets Granovskaia et al. (2010). (B) Transcription factor binding dataset Harbison et al. (2004). (C) Protein-protein interaction dataset from BioGRID Stark et al. (2006).

## References

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## Supplemental Material:

The online version of this article (DOI: 10.1515/sagmb-2016-0016) offers supplementary material, available to authorized users.

Corresponding author: Michael P.H. Stumpf, Theoretical Systems Biology Group, Centre for Bioinformatics, Imperial College London, South Kensington Campus, SW7 2AZ, London, UK, e-mail:

aJustina Žurauskienė and Paul D.W. Kirk should be joint first authors.

Published Online: 2016-03-18

Published in Print: 2016-04-01

Citation Information: Statistical Applications in Genetics and Molecular Biology, Volume 15, Issue 2, Pages 107–122, ISSN (Online) 1544-6115, ISSN (Print) 2194-6302,

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You can create printable tests and worksheets from these Grade 11 Function and Algebra Concepts questions! Select one or more questions using the checkboxes above each question. Then click the add selected questions to a test button before moving to another page.

1 2 3 4 ... 32
Find the next three terms in this sequence: 5120, 1280, 320, 80...
1. -160, -400, -640
2. 20, 5, 1.25
3. 40, 20, 10
4. 76, 72, 68
Solve the quadratic equation $7x^2+1=29$.
2. $x=2$
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Grade 11 Polynomials and Rational Expressions
Which expression is not considered a polynomial?
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What is the constant (c) in the quadratic expression $-350+105i^2$?
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Simplify. Answer must only have positive exponents.

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Simplify.
$(-3x^3)^3$
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$9x^4 + 12x^3 +6x$
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# Printer Setup Using FOG

• Hi all,

I was looking to see if anybody has recently setup printers with FOG. Part of me was thinking that we might as well just use scripts to install said printer drivers, but that would involve replication to each model type in the field for our clients.

Essentially, what is the best practice to deploying and managing printers in FOG, or is best to let Windows handle that portion?

Thanks!

• @x23piracy Again, you should put this stuff into the wiki.

• Hi,

here is one example of my printers:

Alias: KM C258 (AT)
Printer INF File: \\it4005\Treiber\Drucker\KM\C258\KOAYCJ__.INF
Printer IP: 172.19.100.242
Printer Port: IP_172.19.100.242 (It's only the displayname for the port)
Printer Model: KONICA MINOLTA C368SeriesPCL (this is important and have to match the inf file printername)
Printer Config File: \\it4005\Treiber\Drucker\KM\C258\settings.dat (there are vbs scripts that import/export windows printer settings)

the share \it4005\Treiber… is public readable.
If your target systems are win10 try to use drivers from a share the ones embedded for hp are s***

• @Tom-Elliott Correct.

And in cases where drivers are needed that are not present on the systems you’re deploying to - you need to use a share to host the necessary driver, the share needs to be accessible to ANONYMOUS_LOGON because the client will only access it anonymously (because it runs as system). Then you’d plug the FQDN of the shared file into FOG’s configuration for the driver.

• @Raj-G I Think the only requirement is the printer manager use a printer that’s installed on a system.

For example,

Take a system, install the printer. Use the Printer manager and find your newly installed printer. Using the helper tool, copy and paste the information from the manager into the definition in the GUI. It wouldn’t/(shouldn’t?) require server directly.

Sounds good; is there any documentation on that (in terms of what server version should be used, simple setup, etc.)? I don’t remember seeing anything on the Wiki.

Thanks.

• I’ve used FOG with the FOG Client to deploy over 90 printers to 2,000 clients. My recommendation is to absolutely under no circumstance deploy a printer via fog without verifying first that it works. I’ve gone down that road before, it wasn’t fun. Do not let technicians in your organization just do as they please - this is an area that can be screwed up and difficult to recover from.

Setup your printers in FOG - use the FOG Printer Helper program to assist you with figuring out the parameters.

Typically, you would manually install the printer first. Run the FOG Printer Helper program, get the correct parameters it requires, and test deploying the printer via fog to ONE system. If necessary, make available any needed drivers from an anonymous read share.

There’s a lot that goes into FOG Printers - but it can be done, I’ve done it before, several have done it, and you can too.

Hey Wayne,

The FOG Printer Helper program is on the FOG Server (the management dashboard) I assume? From what I’ve seen on the FOG Wiki, the printer setup info seems outdated, but might be similar to what’s in place now?

Like you said, I certainly don’t want to mess this up especially if it breaks during testing.

Thanks!

• I’ve used FOG with the FOG Client to deploy over 90 printers to 2,000 clients. My recommendation is to absolutely under no circumstance deploy a printer via fog without verifying first that it works. I’ve gone down that road before, it wasn’t fun. Do not let technicians in your organization just do as they please - this is an area that can be screwed up and difficult to recover from.

Setup your printers in FOG - use the FOG Printer Helper program to assist you with figuring out the parameters.

Typically, you would manually install the printer first. Run the FOG Printer Helper program, get the correct parameters it requires, and test deploying the printer via fog to ONE system. If necessary, make available any needed drivers from an anonymous read share.

There’s a lot that goes into FOG Printers - but it can be done, I’ve done it before, several have done it, and you can too.

• @Raj-G I use FOG to manage our printers. I have the print drivers stored on a separate nfs server but you could use the image directory on the FOG server as well.

FOG does a good job managing the printers. I have ran into some issues where they printer does not show up in the device list but a reboot of the computer fixes that.


text:
# Tag Info

Well, this is a rather obvious development (in retrospect, that is). We had an $sp^3$ carbon with tetrahedral bonds, and it made diamond. We had an $sp^2$ carbon with trigonal bonds, and it made graphite. What if we just had a linear $sp$ carbon? Such thoughts have been around for more than quite a while. Theorists swarmed around that non-existent tree. No ...


text:
Microbial 'omics

Brought to you by

# hmm-source [artifact]

A HMM-type anvi’o artifact. This artifact is typically provided by the user for anvi’o to import into its databases, process, and/or use.

Back to the main page of anvi’o programs and artifacts.

## Provided by

anvi-script-pfam-accessions-to-hmms-directory

## Description

An HMM source is a collection of one or more hidden Markov models. HMM sources can be used to identify and recover genes in a contigs-db that match to those described in the model.

Models in a given HMM source can be searched in a given contigs-db via the program anvi-run-hmms which would yield an hmm-hits artifact. An anvi’o installation will include multiple HMM sources by default. But HMMs for any set of genes can also be put together by the end user and run on any anvi’o contigs-db.

HMM hits in a contigs-db for a given hmm-source source will be accessible to anvi’o programs globally. Sequences that match to HMM hits can be recovered in an aligned or non-aligned fashion as fasta files for downstream analyses including phylogenomics, they can be displayed in anvi’o interfaces, reported in summary outputs, and so on.

Running anvi-db-info on a contigs-db will list HMM sources available in it.

### Default HMM sources

An anvi’o installation will include multiple HMM sources by default. These HMM sources can be run on any contigs-db with anvi-run-hmms to identify and store hmm-hits:

The default HMM sources in anvi’o include:

• Bacteria_71: 71 single-copy core genes for domain bacteria that represent a modified version of the HMM profiles published by Mike Lee. The anvi’o collection excludes Ribosomal_S20p, PseudoU_synth_1, Exonuc_VII_S, 5-FTHF_cyc-lig, YidD and Peptidase_A8 occurred in Lee collection (as they were exceptionally redundant or rare among MAGs from various habitats), and includes Ribosomal_S3_C, Ribosomal_L5, Ribosomal_L2 to make it more compatible with Hug et al’s set of ribosomal proteins.
• Archaea_76: 76 single-copy core genes for domain archaea by Mike Lee.
• Protista_83: 83 single-copy core genes for protists (domain eukarya) by Tom O. Delmont.

Apart from these, anvi’o also includes a number of HMM profiles for individual ribosomal RNA classes derived from Torsten Seemann’s tool (we split them into individual classes after this):

• Ribosomal_RNA_5S (eukarya + archaea + bacteria; also includes 5.8S).
• Ribosomal_RNA_12S (mitochondria)
• Ribosomal_RNA_16S (bacteria + archaea + mitochondria)
• Ribosomal_RNA_18S (eukarya)
• Ribosomal_RNA_23S (bacteria + archaea)
• Ribosomal_RNA_28S (eukarya)

When anvi-run-hmms is run on an anvi’o contigs-db without providing any further arguments, it automatically utilizes all the default HMM sources.

Similar to Ribosomal RNAs, anvi’o can also identify Transfer RNAs. Even though Transfer RNAs will also appear as an HMM source for all downstream analyses, their initial identification will require running anvi-scan-trnas program on a contigs-db.

### User-defined HMM sources

The user can employ additional HMM sources to identify matching genes in a given contigs-db.

Any directory with expected files in it will serve as an HMM source:

anvi-run-hmms -c contigs-db \ --hmm-source /PATH/TO/USER-HMM-DIRECTORY/

Anvi’o will expect the HMM source directory to contain six files (see this for an example directory). These files are explicitly defined as follows:

• genes.hmm.gz: A gzip of concatenated HMM profiles. One can (1) obtain one or more HMMs by computing them from sequence alignments or by downloading previously computed ones from online resources such as Pfams, (2) concatenate all profiles into a single file called genes.hmm, and finally (3) compress this file using gzip.
• genes.txt: A TAB-delimited file that must contain three columns: gene (gene name), accession (gene accession number (can be anything unique)), and hmmsource (source of HMM profiles listed in genes.hmm.gz). The list of gene names in this file must perfectly match to the list of gene names in genes.hmm.gz.
• kind.txt: A flat text file which contains a single word identifying what type of profile the directory contains. This information will appear in interfaces. Use a single, descriptive word for your collection.
• reference.txt: A file containing source information for this profile to cite it properly.
• target.txt: A file that specifies the target alphabet and context that defines how HMMs should be searched (this is a function of the HMM source that is used). The proper notation is ‘alphabet:context’. Alphabet can be AA, DNA, or RNA. Context can be GENE or CONTIG. The content of this file should be any combination of one alphabet and one context term. For instance, if the content of this file is AA:GENE, anvi’o will search genes amino acid sequences, and so on. An exception is AA:CONTIG, which is an improper target since anvi’o can’t translate contigs to amino acid sequences. See this for more details. Please note that HMMs that target DNA:CONTIG will result in new gene calls in the contigs database to describe their hits.
• noise_cutoff_terms.txt: A file to specify how to deal with noise. See this comment for more information on the contents of this file.

### Creating anvi’o HMM sources from ad hoc PFAM accessions

It is also possible to generate an anvi’o compatible HMMs directory for a given set of PFAM accession ids. For instance, the following command will result in a new directory that can be used immediately with the program anvi-run-hmms:

anvi-script-pfam-accessions-to-hmms-directory --pfam-accessions-list PF00705 PF00706 \ -O AD_HOC_HMMs

These IDs can be given through the command line as a list, or through an input file where every line is a unique accession id.

An example. Let’s assume we have a genome or a metagenome that looks like this:

And we wish to identify locations of genes that match to this model: http://pfam.xfam.org/family/PF06603

One can run this command:

anvi-script-pfam-accessions-to-hmms-directory --pfam-accessions-list PF06603 \ -O UpxZ

which would createa a directory called UpxZ. Then, one would run this command to find matches to this model in a given contigs database:

anvi-run-hmms -c CONTIGS.db \ -H UpxZ/ \ --num-threads 4

Now it is possible to get the sequences matching to this model:

anvi-get-sequences-for-hmm-hits -c CONTIGS.db \ --hmm-source UpxZ \ -o UpxZ.fa

Contigs DB ...................................: Initialized: CONTIGS.db (v. 19)
Hits .........................................: 8 hits for 1 source(s)
Mode .........................................: DNA sequences
Genes are concatenated .......................: False
Output .......................................: UpxZ.fa

Or see where they are by visualizing the project using again:

anvi-interactive -p PROFILE.db \ -c CONTIGS.db

Edit this file to update this information.


text:
# Question

Exhibit 6.19 presents an abbreviated statement of cash flows for Largay Corporation for the current year (amounts in thousands of US\$).
Exhibit 6.19
OPERATIONS
Net Income . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . \$100
Depreciation Expense. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Changes in Working Capital Accounts . . . . . . . . . . . . . . . . . . . . . . . . . . . (40)
Cash Flow from Operations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . \$ 75
INVESTING
Acquisition of Buildings and Equipment . . . . . . . . . . . . . . . . . . . . . . . . . (30)
FINANCING
Repayment of Long-Term Debt . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (40)
Change in Cash . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . \$ 5
Cash, Beginning of Year . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Cash, End of Year . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . \$ 32
After preparing this statement of cash flows for the current year,you discover that the firm sold an item of equipment on the last day of the year but failed to record it in the accounts or to deposit the check received from the purchaser. The equipment originally cost \$50,000 and had accumulated depreciation of \$40,000 at the time of sale. Recast the statement of cash flows in the exhibit, assuming that Largay Corporation sold the equipment for cash in the following amounts (ignore income taxes):
a. \$10,000
b. \$12,000
c. \$8,000

Sales1
Views148


text:
# Latex Matrix

A matrix is defined as a set of numbers called elements arranged in the form of rows and columns so as to from the rectangular array. It has wide applications and are used for various purposes.

The environment is used to implement the matrix, which is given below:

The ampersand (&) symbol separates the columns in the matrix.

We can add as many rows and columns in the matrix according to the requirements.

The rows are separated by the \\ command, which is commonly used to specify the text in the new line.

The matrix environment is implemented using the \ and [.

It is written as:

Without the use of the above environment, the Texmaker will give an error.

Let's understand with a simple example. The example is a 2 x 2 matrix. It is a matrix that has two rows and two columns.

The code for such an example is given below:

Output:

There are different matrix environments used to create different styles of brackets for a matrix, which are listed below:

Environment Surrounding Bracket
pmatrix ( )
Bmatrix { }
bmatrix [ ]
Vmatrix || ||
vmatrix | |

The starred version of the above environments is used to align the columns of the matrix, which is listed below:

Environment Surrounding Bracket
pmatrix* ( )
Bmatrix* { }
bmatrix* [ ]
Vmatrix* || ||
vmatrix* | |

Let's understand the above aligning process by an example. The example is of 3 x 3 matrix having three rows and columns.

The code for such an example is given below:

Output:

You can also design the arbitrary sized matrix. The dots between the matrices can be specified by using the \ddots (⋱), \vdots (⋮), and \cdots (⋯) command.

The code to create such matrix is given below:

Output:

## Matrix with Text

In the running text, we can insert the matrix. The matrix of such type is termed as the small matrix.

The environment used to create small matrix is given below:

But here, we need to specify that the size of text should be greater than that of the matrix.

Let's understand with an example.

The code is given below:

Output:

## Border Matrix

The border matrix is used to create the borders around the matrix. The \bordermatrix command is used to implement such matrices.

The code for such an example is given below:

Output:

## Fraction Matrix

The fraction matrix consists of the fraction elements. We can also insert non-fraction elements according to the requirements.

Let's understand with a simple example. Here, we have used the Vmatrix environment.

The code for such an example is given below:

Output:

## Arrays

The array is similar to the matrix. But here, we can insert lines between rows and columns.

The environment used for such purpose is given below:

Let's understand with two examples.

The code for the first example is given below:

Output:

The code for the second example is given below:

Output:

### Cases

1) The curly brackets in mathematics are defined by using the \left{ and \right} command.

Let's understand by two examples.

The code for the first example is given below:

Output:

2) It is the crucial part of the cases. Here, the cases environment is used to implement such methods, which is written as:

The above environment is commonly used in mathematics to write two equations with certain conditions inside only single brackets.

The code for the second example is given below:

Output:

Next TopicLatex Integral


text:
# Blinking cepheid variable stars in Messier 13

Something that feels like a once in a lifetime event happened here in Bergen this spring. We had four consecutive days of clear skies, with very little wind and no moon!

Earlier on the blog I have expressed the desire to try and image Messier 13 on consecutive nights, to see if I could see the difference in magnitude in the variable stars in the cluster. Especially the variable star V1553 Her, which has a very convenient period of approximately 5 days. 4 days of observing would get me most of the period.

These 4 days were pretty late in spring (30th of March to 2nd or April), and observing had to be done after 10PM in a work week. Not ideal. Thankfully except from the usual tracking problems, there were few problems with the equipment. My own patience failed while doing focusing though, which resulted in two nights with good images, and two with not so great quality.

This was a bit problematic since I wanted to compare images over time, and since I had 40 good images from one night, and 10 from another there was a big difference in the brightness of the stars once I was done stacking images from each night. To account for this I did some brightness matching in post processing matching on the non variable stars of each frame.

The resulting 4 frame time-lapse looks like this.

I was pretty happy with this, as it shows the variability of not only one, but at least one more, and maybe even a third variable star I missed at first (Can you find it? This paper has charts to help). The change in brightness especially for V1553 Her was also much clearer then I expected. Great success!

The process to find the distance to the star from the magnitude and variability data is neat. Since V1553 Her is a Type II Cepheid (how this was determined is not clear to me, please add a comment if you know) which period is approximately 5 days the star has an absolute magnitude of approximately -1.5 according to this chart. The formula below (from here), should then give the distance $$d$$.

$$M_v = m – 2.5log((d/10)^2)$$

Looking at the images and the reference stars, a rough estimate would be that V1553 Her varies between 12 and 13 in apparent magnitude. Plugging in -1.5 for $$M_v$$ and 12.5 for $$m$$ gives the distance of 6310 parsecs, which is 500 parsecs off.

While I have not followed a very thorough process here, it is anyway nice to verify that my data seems to fit to reality. To get better data for deep space objects, I am evaluating to get a solid equatorial mount with either a small refractor or an 8 inch newtonian for imaging, and keep my dobsonian for visual and planetary. Once I do I hope a can revisit this project and get a time-lapse with much higher quality. Maybe do one which would also capture the really fast variables with down to 0.2 days period.


text:
# Successful weight loss can be best accomplished by a. using supplements. b. making small dietary changes over time. c. adhering to short-term diets. d. decreasing energy expenditure.

###### Question:

Successful weight loss can be best accomplished by
a. using supplements.
b. making small dietary changes over time.
d. decreasing energy expenditure.

### Solve: Log5x=log(2x+9)

Solve: Log5x=log(2x+9)...

### I need this done right now and can you help me with other question. question in picture

I need this done right now and can you help me with other question. question in picture...

### What was the treament for ptsd in world war I

what was the treament for ptsd in world war I ...

### Why was Ramon valera proclaimed as national artist?

Why was Ramon valera proclaimed as national artist?...

### Which government decision would best be handled at the state level?

Which government decision would best be handled at the state level?...

### 0.2x10=2 and 2/10=0.2 which type of model do you like best? Why?

0.2x10=2 and 2/10=0.2 which type of model do you like best? Why?...

### What percentage of the survey respondents did not like either soccer or volleyball?

What percentage of the survey respondents did not like either soccer or volleyball?...

### The price of an item has been reduced by 35%. The original was price was 19 %

The price of an item has been reduced by 35%. The original was price was 19 %...

### There is too much traffic in the city. what do you think the authorities should do about it?

there is too much traffic in the city. what do you think the authorities should do about it?...

### (1.6x10^12) divided by (8.01x10^23) =?

(1.6x10^12) divided by (8.01x10^23) =?...

### And the other two is gravity and seconds

And the other two is gravity and seconds...

### What is a public good? (1 point) O A public good is a product or service that one consumer can prevent another consumer from using, and is not accessible without payment. A public good is a product or service that one consumer cannot prevent another consumer from using, and is not accessible without payment. A public good is a product or service that one consumer cannot prevent another consumer from using, and is accessible without payment. A public good is a product or service that one consumer

What is a public good? (1 point) O A public good is a product or service that one consumer can prevent another consumer from using, and is not accessible without payment. A public good is a product or service that one consumer cannot prevent another consumer from using, and is not accessible without...

### Now, fill in the blanks in the following sentences with the correct forms of the verbs in parentheses. El profesor enseñ Symbols la lección. (enseñar)

Now, fill in the blanks in the following sentences with the correct forms of the verbs in parentheses. El profesor enseñ Symbols la lección. (enseñar)...

### How do u friend people

How do u friend people...

### The purpose of the Sherman Antitrust Act was to Select one:_______. a. encourage competition by restraining the growth of monopolies. b. standardize the level of competition. c. encourage the growth of large-scale efficiency found in big businesses. d. minimize the inconsistency of multiple dealers of a single product.

The purpose of the Sherman Antitrust Act was to Select one:_______. a. encourage competition by restraining the growth of monopolies. b. standardize the level of competition. c. encourage the growth of large-scale efficiency found in big businesses. d. minimize the inconsistency of multiple dealers ...

### Which of the following statements about check cashing companies is FALSE? They can take a percentage of your check on top of fees. They charge low fees. They offer bad deals where you'll owe a lot more than you borrowed. They make it easy to fall into a loan cycle that is hard to get out of.

Which of the following statements about check cashing companies is FALSE? They can take a percentage of your check on top of fees. They charge low fees. They offer bad deals where you'll owe a lot more than you borrowed. They make it easy to fall into a loan cycle that is hard to get out of....

### Is the product of two mixed numbers less than between or greater than two factors

Is the product of two mixed numbers less than between or greater than two factors...


text:
Algebra word problem (Red and Yellow Jelly Beans)

A jar contains some red and some yellow jelly beans. If a child ate 1 red jelly bean, 1/7 of the remaining candies would be red. If instead the child ate 5 yellow jelly beans, 1/6 of the remaining candies would be red. How do I found out the number of jelly beans that are in the jar?

-
What have you tried so far? –  Oscar Cunningham Jan 18 '11 at 0:14
This has nothing to do with probability. –  Aryabhata Jan 18 '11 at 0:15
@user5962: How is this a probability question? –  user17762 Jan 18 '11 at 0:17
It is not "linear algebra" either. –  Andres Caicedo Jan 18 '11 at 0:21
@Andres: Well, 2 linear equations, 2 variables :-) –  Aryabhata Jan 18 '11 at 0:25

HINT $\$ Put $\rm R =$ #red beans. Then the total #beans $\rm\: =\ 7\ (R-1) + 1\ =\ 6\ R + 5\:.$

-
thank you very much –  user5962 Jan 18 '11 at 1:36

Use algebra.

Let R be the number of red beans, and Y be the number of yellow beans. Then the second and third sentences can be expressed as equations in R and Y. Solve this pair of equations, and you've got it.

For instance, the second sentence tells us that $\frac{R-1}{R+Y-1}=\frac{1}{7}$.

-
thank you very much! –  user5962 Jan 18 '11 at 0:20


text:
One of the more famous identities that Euler discovered was the identity relating the five great constants of mathematics:

These five constants of nature, Euler discovered, could neatly be tied together in a single, simple equation:

Note that the identity also uses three fundamental operations of arithmetic (as extended to complex numbers):

The proof of Euler's identity is trivial if one uses the more generalized Euler's formula.

## Algebra

Algebraic manipulations of this simple identity can demonstrate each of the five constants in terms of the other four:

These above equivalences are greatly applicable as substitutions in more complex mathematics. For example, evaluating the logarithms of negative values:

Thus, the natural logarithm of a negative real value, , is a complex number: