English

Clustering algorithms play a pivotal role in data mining, offering powerful tools for uncovering hidden patterns and structures within datasets. These algorithms aim to divide data points into coherent groups based on similarities or dissimilarities, making it easier to explore and understand complex data. Clustering algorithms typically rely on similarity measures to assess the likeness between data points. Consequently, selecting a suitable similarity measure is crucial for achieving satisfactory clustering outcomes. However, this decision can pose significant challenges, especially for non-experts, given the plethora of similarity measures available in the literature and their performance which is closely linked to the specific dataset, clustering algorithm, and cluster validity index employed. This difficulty is even more important when considering mixed data clustering. Mixed data refers to heterogeneous data characterized by both numerical and categorical attributes. In such a context, the same similarity measure cannot be used for both types of attributes due to their different nature. Commonly, two similarity measures are combined, one for numerical attributes and one for categorical attributes. This adds a layer of complexity to the problem since it requires the selection of two similarity measures instead of just one. This paper introduces SIMREC, a similarity measure recommendation system for mixed data clustering. The system uses meta-learning to mine the relationship between dataset characteristics and similarity measures performances for different mixed data clustering algorithms and cluster validity indices. Therefore, given a mixed dataset, a mixed data clustering algorithm, and a cluster validity index, the system can recommend suitable pairs of numerical and categorical similarity measures based on the characteristics of the dataset. We implemented the proposed system using 130 pairs of similarity measures (10 numerical and 13 categorical), 4 commonly used mixed data clustering algorithms (K-Prototypes, LSH-K-Prototypes, K-Medoids, and Hierarchical Clustering), and three cluster validity indices (Silhouette, Clustering Accuracy, and Adjusted Rand Index). Our experiments on 185 publicly available mixed datasets show that the pairs of similarity measures recommended by SIMREC outperform the baseline pairs, including classically used pairs of similarity measures in the literature.

BackgroundSerial Analysis of Gene Expression (SAGE) is a DNA sequencing-based method for large-scale gene expression profiling that provides an alternative to microarray analysis. Most analyses of SAGE data aimed at identifying co-expressed genes have been accomplished using various versions of clustering approaches that often result in a number of false positives.Principal FindingsHere we explore the use of seriation, a statistical approach for ordering sets of objects based on their similarity, for large-scale expression pattern discovery in SAGE data. For this specific task we implement a seriation heuristic we term ‘progressive construction of contigs’ that constructs local chains of related elements by sequentially rearranging margins of the correlation matrix. We apply the heuristic to the analysis of simulated and experimental SAGE data and compare our results to those obtained with a clustering algorithm developed specifically for SAGE data. We show using simulations that the performance of seriation compares favorably to that of the clustering algorithm on noisy SAGE data.ConclusionsWe explore the use of a seriation approach for visualization-based pattern discovery in SAGE data. Using both simulations and experimental data, we demonstrate that seriation is able to identify groups of co-expressed genes more accurately than a clustering algorithm developed specifically for SAGE data. Our results suggest that seriation is a useful method for the analysis of gene expression data whose applicability should be further pursued.

Fuzzy C-Means (FCM) algorithm has been widely used in cluster analysis of gene expression data. It can converge rapidly and provide more information regarding relationships within the data thanks to the usage of fuzzy sets to represent the degrees of cluster membership for every data point. However, FCM has a shortcoming in that it requires a priori specification of cluster number and cluster validation. Most cluster validity indices are based on the data themselves and may not be applicable for gene expression data. In this paper, we propose a Bayesian method using Gene Ontology (GO) annotations for gene expression cluster validation. We show that our method outperforms popular validity indices on gene expression datasets.

Use of a fuzzy granulation–degranulation criterion for assessing cluster validity

Clustering is a useful exploratory technique for the analysis of gene expression data. Many different heuristic clustering algorithms have been proposed in this context. Clustering algorithms based on probability models offer a principled alternative to heuristic algorithms. In particular, model-based clustering assumes that the data is generated by a finite mixture of underlying probability distributions such as multivariate normal distributions. The issues of selecting a 'good' clustering method and determining the 'correct' number of clusters are reduced to model selection problems in the probability framework. Gaussian mixture models have been shown to be a powerful tool for clustering in many applications. We benchmarked the performance of model-based clustering on several synthetic and real gene expression data sets for which external evaluation criteria were available. The model-based approach has superior performance on our synthetic data sets, consistently selecting the correct model and the number of clusters. On real expression data, the model-based approach produced clusters of quality comparable to a leading heuristic clustering algorithm, but with the key advantage of suggesting the number of clusters and an appropriate model. We also explored the validity of the Gaussian mixture assumption on different transformations of real data. We also assessed the degree to which these real gene expression data sets fit multivariate Gaussian distributions both before and after subjecting them to commonly used data transformations. Suitably chosen transformations seem to result in reasonable fits. MCLUST is available at http://www.stat.washington.edu/fraley/mclust. The software for the diagonal model is under development. kayee@cs.washington.edu. http://www.cs.washington.edu/homes/kayee/model.

Today, DNA microarray technology is the most widely employed functional genomics approach in the bioinformatics domain. Disclosing the patterns masked in gene expression data provides an opportunity for an enhanced comprehension of functional genomics. But, the large number of genes and the intricate biological networks has greatly increased the challenges of comprehending and interpreting the resulting mass of data, which often contains millions of measurements. So, clustering techniques are used to tackle this challenge. Several clustering techniques have been developed and used in the analysis of microarray data. But, such techniques are not much efficient in analyzing the gene expression data. In this paper, we propose a novel efficient hybrid clustering approach based on quad tree data structure. In the hierarchical clustering process, the creation of the closest pair data structure in each level is an important time factor that provides the processing time of clustering. Here, a quad tree based data structure is used for identifying the closest pair elements. Thus, the proposed approach reduces the processing time successfully and offers a better analysis of gene expression data.

DNA Microarray Technique Current Analytical Methods of DNA Microarray Data Advantages and Disadvantages Current Application of DNA Microarray Technique in Medicine A Novel Method for DNA Microarray Data Analysis Future Directions.

There is a growing need for a method to analyze massive gene expression data obtained from DNA microarrays. We introduce a method of combining a self-organizing map (SOM) and a k-means clustering for analyzing and categorizing the gene expression data. The SOM is an unsupervised neural network learning algorithm and forms a mapping the high-dimensional data to two-dimensional space. However, it is difficult to find clustering boundaries from results of the SOM. On the other hand, the k-means clustering can partition the data into the clusters under the assumption of the known number of clusters. In order to understand easily the results of SOM, we apply the k-means clustering to finding the clustering boundaries from results of SOM. We have applied the proposed method to the published data of yeast gene expression and show that the method is effective for categorizing the data.

BackgroundClustering methods are widely used on gene expression data to categorize genes with similar expression profiles. Finding an appropriate (dis)similarity measure is critical to the analysis. In our study, we developed a new measure for clustering the genes when the key factor is the shape of the profile, and when the expression magnitude should also be accounted for in determining the gene relationship. This is achieved by modeling the shape and magnitude parameters separately in a gene expression profile, and then using the estimated shape and magnitude parameters to define a measure in a new feature space.ResultsWe explored several different transformation schemes to construct the feature spaces that include a space whose features are determined by the mutual differences of the original expression components, a space derived from a parametric covariance matrix, and the principal component space in traditional PCA analysis. The former two are the newly proposed and the latter is explored for comparison purposes. The new measures we defined in these feature spaces were employed in a K-means clustering procedure to perform analyses. Applying these algorithms to a simulation dataset, a developing mouse retina SAGE dataset, a small yeast sporulation cDNA dataset, and a maize root affymetrix microarray dataset, we found from the results that the algorithm associated with the first feature space, named TransChisq, showed clear advantages over other methods.ConclusionThe proposed TransChisq is very promising in capturing meaningful gene expression clusters. This study also demonstrates the importance of data transformations in defining an efficient distance measure. Our method should provide new insights in analyzing gene expression data. The clustering algorithms are available upon request.

Class discovery from gene expression data is an important task for cancer diagnosis. In this paper, we present a new framework for class discovery. The new framework integrates the perturbation technique, the cluster ensemble approach, and the cluster validity index. Specifically, it first generates a set of perturbed datasets from the original microarray data. Then, the Neural Gas, which serves as the basic clustering algorithm, is applied to obtain the partitions from the original dataset and the perturbed datasets. Finally, a new cluster validity index called disagreement/agreement (DA) index (DAI) is designed to identify the number of classes in the dataset by considering the difference between the partition obtained from the original dataset and the partitions obtained from the perturbed datasets. The experiments in three synthetic datasets and four cancer datasets show that: 1) DAI successfully discovers the underlying structure from all the synthetic datasets and most of the cancer datasets and 2) DAI outperforms most of the state-of-the-art cluster validity indexes when applied to gene expression data.

There are two notoriously hard problems in cluster analysis, estimating the number of clusters, and checking whether the population to be clustered is not actually homogeneous. Given a dataset, a clustering method and a cluster validation index, this paper proposes to set up null models that capture structural features of the data that cannot be interpreted as indicating clustering. Artificial datasets are sampled from the null model with parameters estimated from the original dataset. This can be used for testing the null hypothesis of a homogeneous population against a clustering alternative. It can also be used to calibrate the validation index for estimating the number of clusters, by taking into account the expected distribution of the index under the null model for any given number of clusters. The approach is illustrated by three examples, involving various different clustering techniques (partitioning around medoids, hierarchical methods, a Gaussian mixture model), validation indexes (average silhouette width, prediction strength and BIC), and issues such as mixed type data, temporal and spatial autocorrelation.

Analysis of covariance patterns in gene expression data and FT-IR spectra

Procedures that evaluate the results of clustering algorithms are known as cluster validation (CV) indexes. There exist several CV indexes usually classified into two broad classes namely external and internal clustering validation indexes depending on whether ground truth or optimal clustering solutions are known in advance or not respectively. Traditional cluster validation indexes are even impossible to perform especially when the size of the data set is very large. To solve the issue of CV indexes in such contexts, we propose parallel and distributed external clustering validation models based on MapReduce for three indexes namely: F-measure, Normalized Mutual Information and Variation of Information. The experimental results reveal that these models scale very well with increasing size of dataset and provide accurate results.

Many clustering algorithms have been proposed for the analysis of gene expression data, but little guidance is available to help choose among them. We provide a systematic framework for assessing the results of clustering algorithms. Clustering algorithms attempt to partition the genes into groups exhibiting similar patterns of variation in expression level. Our methodology is to apply a clustering algorithm to the data from all but one experimental condition. The remaining condition is used to assess the predictive power of the resulting clusters-meaningful clusters should exhibit less variation in the remaining condition than clusters formed by chance. We successfully applied our methodology to compare six clustering algorithms on four gene expression data sets. We found our quantitative measures of cluster quality to be positively correlated with external standards of cluster quality.

Background - In the NeoTRIPaPDL1 phase III trial, triple-negative breast cancer (TNBC) patients were randomized to receive nab-paclitaxel/carboplatin for 8 cycles (CT arm) with or without atezolizumab (CT/A arm). We previously reported that the majority of patients (65%) with PD-L1- at baseline converted to PD-L1+ (the majority with IC2/IC3) after the first cycle of treatment in the atezolizumab arm. Here we studied treatment associated changes in the molecular tumour features and immune microenvironment by PD-L1 expression. Methods – A total of 158 (56.4%) of patients enrolled in the NeoTRIPaPDL1 trial (76 and 82 from CT/A and CT arm, respectively) were included in this analysis by satisfying the following criteria: i) availability of a paired core biopsy at baseline and at day 1 of the second treatment cycle (D1C2); ii) evaluation of stromal TILs (sTILs) and staining for PD-L1 (Ventana SP142); iii) successful RNA-seq gene expression profiling. PD-L1 groups were defined as IC0/IC1 (<5% PD-L1low) vs IC2/IC3 (>=5% PD-L1high). Presence of different immune cell populations was quantified by gene expression profile deconvolution using ConsensusTME R package. Cancer hallmark gene set collection and custom signature activation status were estimated in each sample using singscore R package. Differences in score distribution were evaluated by 2-sided t-test. Results At baseline, both sTILs and immune cell signatures were upregulated in PD-L1high compared to PD-L1low tumours (p<0.001). No significant differences were found between the two treatment arms in the PD-L1high subpopulation. In the PD-L1low cases, both sTILs and immune related signatures were slightly downregulated in the CT/A arm (p<0.05), suggesting a modest unbalance among treatment arms with CT arm being slightly more inflamed than CT/A arm.At D1C2, PD-L1high tumours in the CT arm systematically had high sTILs (median=70%, range=30-90%), while PD-L1low tumours receiving CT/A had low sTILs in a significant proportion of cases (median=30%, range=0-90%; p<0.001). Similarly, at D1C2 several gene expression-estimated immune cell populations and immune-related signatures were upregulated in the CT arm compared to CT/A arm in PD-L1high tumours, with the weakest association observed for M2 macrophages (p=0.058). No tumour-related signatures were differentially expressed among the two treatment arms within groups with PD-L1high, suggesting that different treatment. modulate PD-L1 by engaging a different immune mileau instead of modulating tumor related features.Considering PD-L1low groups at D1C2, in the CT arm 21 tumors had >30% sTILs (n=21/69, 30.4%), while in the CT/A arm only 2 had sTILs >30% (2/27, 7.4%) (p<0.001). Analysis of gene expression data identified IFN-related signatures as the most upregulated in the CT compared to CT/A arm in PD-L1low cases at D1C2 (p<0.05). Conclusions Integrated dynamic analysis of PD-L1 expression and gene expression data highlighted significant treatment-specific changes of the immune landscape according to PD-L1 expression, when this biomarker is assessed during treatment. This indicates that the immune milieu associated with PD-L1 status is strongly dependent on the time of assessment in relationship to treatment received. Such observation may explain why in the NeoTRIP trial, baseline PD-L1 but not on-treatment PD-L1 was predictive of pCR in CT/A arm. In addition, our findings could have implications related to the use of PD-L1 as a predictive biomarker in pre-treated patients, especially when assessed early on during treatment. Citation Format: Maurizio Callari, Chiun-Sheng Huang, Daniel Egle, Begoña Bermejo, Claudio Zamagni, Matteo Dugo, Marc Thill, Antonio Anton, Marco Barreca, Stefania Russo, Eva Maria Ciruelos, Richard Greil, Stefania Zambelli, Balázs Gyorffy, Chanel Smart, Olivia Biasi, Pinuccia Valagussa, Giuseppe Viale, Luca Gianni, Giampaolo Bianchini. Immune milieu associated with PD-L1 status in TNBC is dependent on time of biomarker assessment and treatment received: A secondary analysis of the NeoTRIPaPDL1 trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-04-02.