3D clustering of gene expression data from systemic autoinflammatory diseases using self-organizing maps (Clust3D).

Background and objective: Systemic autoinflammatory diseases (SAIDs) are characterized by widespread inflammation, but for most of them there is a lack of specific biomarkers for accurate diagnosis. Although a number of machine learning algorithms have been used to analyze SAID datasets, aiding in the discovery of novel biomarkers, there is a growing recognition of the importance of SAID timeseries clustering, as it can capture the temporal dynamics of gene expression patterns. Methodology: This paper proposes a novel clustering methodology to efficiently associate three-dimensional data. The algorithm utilizes competitive learning to create a self-organizing neural network and adjust neuron positions in time-dependent and high dimensional feature space in order to assign them as clustering centers. The quantitative evaluation of the clustering was based on well-known clustering indices. Furthermore, a differential expression analysis and classification pipeline was employed to assess the capability of the proposed methodology to extract more accurate pathway-specific genes from its clusters. For that, a comparative analysis was also conducted against a heuristic timeseries clustering method. Results: The proposed methodology achieved better overall clustering indices scores and classification metrics using genes derived from its clusters. Notable cases include a threefold increase in the Calinski-Harabasz clustering index, a twofold improvement in the Davies-Bouldin clustering index and a ∼60% increase in the classification specificity score. Conclusion: A novel clustering methodology was developed and applied on several gene expression timeseries datasets from systemic autoinflammatory diseases, and its ability to efficiently produce well separated clusters compared to existing heuristic methods was demonstrated.

Classification of Inflammation of Unknown Origin patients based on RNA-seq and SomaScan data.

A preliminary analysis was conducted on data acquired from RNA sequencing and SomaScan platforms, for the classification of patients with Inflammation of Unknown Origin. To this end, a multimodal data integration approach was designed, by combining the two platforms, in order to assess the potentiality of learning estimators, using the differentially expressed features from the independent profiling experiments of both platforms. The classification framing was the differentiation of Inflammation of Unknown Origin patients against a multitude of Systemic Autoinflammatory disease patients. Separate false discovery rate analyses were performed on each dataset to extract statistically significant features between the two designated sample groups. Genomic analysis managed higher overall classification metrics compared to proteomic analysis, averaging an ~19% increase overall metrics and classifiers, with a ~0.07% increase in standard error. The multimodal data integration approach achieved similar results to the individual platforms' analyses. More specifically, it managed the same classification accuracy, sensitivity, and specificity scores as the best individual analysis, with the simple Logistic Regression estimator.Clinical Relevance- This study highlights the advantage of exploiting RNA sequencing data to identify potential Inflammation of Unknown Origin disease specific biomarkers, even against other Systemic Autoinflammatory diseases. These findings are further emphasized given the non-apparent clinical discrepancy between Inflammation of Unknown Origin and other Systemic Autoinflammatory diseases.

Comparison of High-Throughput Technologies in the Classification of Adult-Onset Still's Disease Patients.

A meta-analysis study was conducted to compare high-throughput technologies in the classification of Adult-Onset Still's Disease patients, using differentially expressed genes from independent profiling experiments. We exploited two publicly available datasets from the Gene Expression Omnibus and performed a separate differential expression analysis on each dataset to extract statistically important genes. We then mapped the genes of the two datasets and subsequently we employed well-established machine learning algorithms to evaluate the denoted genes as candidate biomarkers. Using next-generation sequencing data, we managed to achieve the maximum (100%) classification accuracy, sensitivity and specificity with the Gradient Boosting and the Random Forest classifiers, compared to the 83% of the DNA microarray data. Clinical Relevance- When biomarkers derived from one study are applied to the data of another, in many cases the results may diverge significantly. Here we establish that in cross-profiling meta-analysis approaches based on differential expression analysis, next-generation sequencing data provide more accurate results than microarray experiments in the classification of Adult-Onset Still's Disease patients.