Vijay V. Raghavan

Poorya Khajouie, Titli Sarkar, Krishna Rauniyar et al.

Protein structures represent the key to deciphering biological functions. The more detailed form of similarity among these proteins is sometimes overlooked by the conventional structural comparison methods. In contrast, further advanced methods, such as Triangular Spatial Relationship (TSR), have been demonstrated to make finer differentiations. Still, the classical implementation of TSR does not provide for the integration of secondary structure information, which is important for a more detailed understanding of the folding pattern of a protein. To overcome these limitations, we developed the SSE-TSR approach. The proposed method integrates secondary structure elements (SSEs) into TSR-based protein representations. This allows an enriched representation of protein structures by considering 18 different combinations of helix, strand, and coil arrangements. Our results show that using SSEs improves the accuracy and reliability of protein classification to varying degrees. We worked with two large protein datasets of 9.2K and 7.8K samples, respectively. We applied the SSE-TSR approach and used a neural network model for classification. Interestingly, introducing SSEs improved performance statistics for Dataset 1, with accuracy moving from 96.0% to 98.3%. For Dataset 2, where the performance statistics were already good, further small improvements were found with the introduction of SSE, giving an accuracy of 99.5% compared to 99.4%. These results show that SSE integration can dramatically improve TSR key discrimination, with significant benefits in datasets with low initial accuracies and only incremental gains in those with high baseline performance. Thus, SSE-TSR is a powerful bioinformatics tool that improves protein classification and understanding of protein function and interaction.

Murat Seckin Ayhan, Vijay Raghavan, Alzheimer's disease Neuroimaging Initiative

Alzheimer's disease is a major cause of dementia. Its diagnosis requires accurate biomarkers that are sensitive to disease stages. In this respect, we regard probabilistic classification as a method of designing a probabilistic biomarker for disease staging. Probabilistic biomarkers naturally support the interpretation of decisions and evaluation of uncertainty associated with them. In this paper, we obtain probabilistic biomarkers via Gaussian Processes. Gaussian Processes enable probabilistic kernel machines that offer flexible means to accomplish Multiple Kernel Learning. Exploiting this flexibility, we propose a new variation of Automatic Relevance Determination and tackle the challenges of high dimensionality through multiple kernels. Our research results demonstrate that the Gaussian Process models are competitive with or better than the well-known Support Vector Machine in terms of classification performance even in the cases of single kernel learning. Extending the basic scheme towards the Multiple Kernel Learning, we improve the efficacy of the Gaussian Process models and their interpretability in terms of the known anatomical correlates of the disease. For instance, the disease pathology starts in and around the hippocampus and entorhinal cortex. Through the use of Gaussian Processes and Multiple Kernel Learning, we have automatically and efficiently determined those portions of neuroimaging data. In addition to their interpretability, our Gaussian Process models are competitive with recent deep learning solutions under similar settings.