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Leukemia multiclass assessment and classification from Microarray and RNA-seq technologies integration at gene expression level.

ABSTRACT: In more recent years, a significant increase in the number of available biological experiments has taken place due to the widespread use of massive sequencing data. Furthermore, the continuous developments in the machine learning and in the high performance computing areas, are allowing a faster and more efficient analysis and processing of this type of data. However, biological information about a certain disease is normally widespread due to the use of different sequencing technologies and different manufacturers, in different experiments along the years around the world. Thus, nowadays it is of paramount importance to attain a correct integration of biologically-related data in order to achieve genuine benefits from them. For this purpose, this work presents an integration of multiple Microarray and RNA-seq platforms, which has led to the design of a multiclass study by collecting samples from the main four types of leukemia, quantified at gene expression. Subsequently, in order to find a set of differentially expressed genes with the highest discernment capability among different types of leukemia, an innovative parameter referred to as coverage is presented here. This parameter allows assessing the number of different pathologies that a certain gen is able to discern. It has been evaluated together with other widely known parameters under assessment of an ANOVA statistical test which corroborated its filtering power when the identified genes are subjected to a machine learning process at multiclass level. The optimal tuning of gene extraction evaluated parameters by means of this statistical test led to the selection of 42 highly relevant expressed genes. By the use of minimum-Redundancy Maximum-Relevance (mRMR) feature selection algorithm, these genes were reordered and assessed under the operation of four different classification techniques. Outstanding results were achieved by taking exclusively the first ten genes of the ranking into consideration. Finally, specific literature was consulted on this last subset of genes, revealing the occurrence of practically all of them with biological processes related to leukemia. At sight of these results, this study underlines the relevance of considering a new parameter which facilitates the identification of highly valid expressed genes for simultaneously discerning multiple types of leukemia.

SUBMITTER: Castillo D

PROVIDER: S-EPMC6372182 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundNowadays, many public repositories containing large microarray gene expression datasets are available. However, the problem lies in the fact that microarray technology are less powerful and accurate than more recent Next Generation Sequencing technologies, such as RNA-Seq. In any case, information from microarrays is truthful and robust, thus it can be exploited through the integration of microarray data with RNA-Seq data. Additionally, information extraction and acquisition of large number of samples in RNA-Seq still entails very high costs in terms of time and computational resources.This paper proposes a new model to find the gene signature of breast cancer cell lines through the integration of heterogeneous data from different breast cancer datasets, obtained from microarray and RNA-Seq technologies. Consequently, data integration is expected to provide a more robust statistical significance to the results obtained. Finally, a classification method is proposed in order to test the robustness of the Differentially Expressed Genes when unseen data is presented for diagnosis.ResultsThe proposed data integration allows analyzing gene expression samples coming from different technologies. The most significant genes of the whole integrated data were obtained through the intersection of the three gene sets, corresponding to the identified expressed genes within the microarray data itself, within the RNA-Seq data itself, and within the integrated data from both technologies. This intersection reveals 98 possible technology-independent biomarkers. Two different heterogeneous datasets were distinguished for the classification tasks: a training dataset for gene expression identification and classifier validation, and a test dataset with unseen data for testing the classifier. Both of them achieved great classification accuracies, therefore confirming the validity of the obtained set of genes as possible biomarkers for breast cancer. Through a feature selection process, a final small subset made up by six genes was considered for breast cancer diagnosis.ConclusionsThis work proposes a novel data integration stage in the traditional gene expression analysis pipeline through the combination of heterogeneous data from microarrays and RNA-Seq technologies. Available samples have been successfully classified using a subset of six genes obtained by a feature selection method. Consequently, a new classification and diagnosis tool was built and its performance was validated using previously unseen samples.

Project description:Most of the research studies developed applying microarray technology to the characterization of different pathological states of any disease may fail in reaching statistically significant results. This is largely due to the small repertoire of analysed samples, and to the limitation in the number of states or pathologies usually addressed. Moreover, the influence of potential deviations on the gene expression quantification is usually disregarded. In spite of the continuous changes in omic sciences, reflected for instance in the emergence of new Next-Generation Sequencing-related technologies, the existing availability of a vast amount of gene expression microarray datasets should be properly exploited. Therefore, this work proposes a novel methodological approach involving the integration of several heterogeneous skin cancer series, and a later multiclass classifier design. This approach is thus a way to provide the clinicians with an intelligent diagnosis support tool based on the use of a robust set of selected biomarkers, which simultaneously distinguishes among different cancer-related skin states. To achieve this, a multi-platform combination of microarray datasets from Affymetrix and Illumina manufacturers was carried out. This integration is expected to strengthen the statistical robustness of the study as well as the finding of highly-reliable skin cancer biomarkers. Specifically, the designed operation pipeline has allowed the identification of a small subset of 17 differentially expressed genes (DEGs) from which to distinguish among 7 involved skin states. These genes were obtained from the assessment of a number of potential batch effects on the gene expression data. The biological interpretation of these genes was inspected in the specific literature to understand their underlying information in relation to skin cancer. Finally, in order to assess their possible effectiveness in cancer diagnosis, a cross-validation Support Vector Machines (SVM)-based classification including feature ranking was performed. The accuracy attained exceeded the 92% in overall recognition of the 7 different cancer-related skin states. The proposed integration scheme is expected to allow the co-integration with other state-of-the-art technologies such as RNA-seq.

Project description:Motor imagery (MI) allows the design of self-paced brain-computer interfaces (BCIs), which can potentially afford an intuitive and continuous interaction. However, the implementation of non-invasive MI-based BCIs with more than three commands is still a difficult task. First, the number of MIs for decoding different actions is limited by the constraint of maintaining an adequate spacing among the corresponding sources, since the electroencephalography (EEG) activity from near regions may add up. Second, EEG generates a rather noisy image of brain activity, which results in a poor classification performance. Here, we propose a solution to address the limitation of identifiable motor activities by using combined MIs (i.e., MIs involving 2 or more body parts at the same time). And we propose two new multilabel uses of the Common Spatial Pattern (CSP) algorithm to optimize the signal-to-noise ratio, namely MC2CMI and MC2SMI approaches. We recorded EEG signals from seven healthy subjects during an 8-class EEG experiment including the rest condition and all possible combinations using the left hand, right hand, and feet. The proposed multilabel approaches convert the original 8-class problem into a set of three binary problems to facilitate the use of the CSP algorithm. In the case of the MC2CMI method, each binary problem groups together in one class all the MIs engaging one of the three selected body parts, while the rest of MIs that do not engage the same body part are grouped together in the second class. In this way, for each binary problem, the CSP algorithm produces features to determine if the specific body part is engaged in the task or not. Finally, three sets of features are merged together to predict the user intention by applying an 8-class linear discriminant analysis. The MC2SMI method is quite similar, the only difference is that any of the combined MIs is considered during the training phase, which drastically accelerates the calibration time. For all subjects, both the MC2CMI and the MC2SMI approaches reached a higher accuracy than the classic pair-wise (PW) and one-vs.-all (OVA) methods. Our results show that, when brain activity is properly modulated, multilabel approaches represent a very interesting solution to increase the number of commands, and thus to provide a better interaction.

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Leukemia multiclass assessment and classification from Microarray and RNA-seq technologies integration at gene expression level.

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