A protein family has similar and diverse functions locally conserved as aligned sequence segments. Further discovering their association patterns could reveal subtle family subgroup characteristics. Since aligned residues associations (ARAs) in Aligned Pattern Clusters (APCs) are complex and intertwined due to entangled function, factors, and variance in the source environment, we have recently developed a novel method: Aligned Residue Association Discovery and Disentanglement (ARADD) to solve this problem. ARADD first obtains from an APC an ARA Frequency Matrix and converts it to an adjusted statistical residual vector space (SRV). It then disentangles the SRV into Principal Components (PCs) and Re-projects their vectors to a SRV to reveal succinct orthogonal AR groups. In this study, we applied ARADD to class A scavenger receptors (SR-A), a subclass of a diverse protein family binding to modified lipoproteins with diverse biological functionalities not explicitly known. Our experimental results demonstrated that ARADD can unveil subtle subgroups in sequence segments with diverse functionality and highly variable sequence lengths. We also demonstrated that the ARAs captured in a Position Weight Matrix or an APC were entangled in biological function and domain location but disentangled by ARADD to reveal different subclasses without knowing their actual occurrence positions.

A protein family has similar and diverse functions locally conserved. An aligned pattern cluster (APC) can reflect the conserved functionality. Discovering aligned residue associations (ARAs) in APCs can reveal subtle inner working characteristics of conserved regions of protein families. However, ARAs corresponding to different functionalities/subgroups/classes could be entangled because of subtle multiple entwined factors. To discover and disentangle patterns from mixed-mode datasets, such as APCs when the residues are replaced by their fundamental biochemical properties list, this paper presents a novel method, Extended Aligned Residual Association Discovery and Disentanglement (E-ARADD). E-ARADD discretizes the numerical dataset to transform the mixed-mode dataset into an event-value dataset, constructs an ARA Frequency Matrix and then converts it into an adjusted Statistical Residual (SR) Vector Space (SRV) capturing statistical deviation from randomness. By applying Principal Component (PC) Decomposition on SRV, PCs ranked by their variance are obtained. Finally, the disentangled ARAs are discovered when the projections on a PC is re-projected to a vector space with the same basis vectors of SRV. Experiments on synthetic, cytochrome c and class A scavenger data have shown that E-ARADD can a) disentangle the entwined ARAs in APCs (with residues or biochemical properties), b) reveal subtle AR clusters relating to classes, subtle subgroups or specific functionalities. E-ARADD can discover and disentangle ARs and ARAs entangled in functionality and location of protein families to reveal functional subgroups and subgroup characteristics of biological conserved regions. Experimental results on synthetic data provides the proof-of-concept validation on the successful disentanglement that reveals class-associated ARAs with or without class labels as input. Experiments on cytochrome c data proved the efficacy of E-ARADD in handing both types of residue data. Our novel methodology is not only able to discover and disentangle ARs and ARAs in specific statistical/functional (PCs and RSRVs) spaces, but also their locations in the protein family functional domains. The success of E-ARADD shows its great potential to proteomic research, drug discovery and precision and personalized genetic medicine.

A Content-Based Image Retrieval (CBIR) system which identifies similar medical images based on a query image can assist clinicians for more accurate diagnosis. The recent CBIR research trend favors the construction and use of binary codes to represent images. Deep architectures could learn the non-linear relationship among image pixels adaptively, allowing the automatic learning of high-level features from raw pixels. However, most of them require class labels, which are expensive to obtain, particularly for medical images. The methods which do not need class labels utilize a deep autoencoder for binary hashing, but the code construction involves a specific training algorithm and an ad-hoc regularization technique. In this study, we explored using a deep de-noising autoencoder (DDA), with a new unsupervised training scheme using only backpropagation and dropout, to hash images into binary codes. We conducted experiments on more than 14,000 x-ray images. By using class labels only for evaluating the retrieval results, we constructed a 16-bit DDA and a 512-bit DDA independently. Comparing to other unsupervised methods, we succeeded to obtain the lowest total error by using the 512-bit codes for retrieval via exhaustive search, and speed up 9.27 times with the use of the 16-bit codes while keeping a comparable total error. We found that our new training scheme could reduce the total retrieval error significantly by 21.9%. To further boost the image retrieval performance, we developed Radon Autoencoder Barcode (RABC) which are learned from the Radon projections of images using a de-noising autoencoder. Experimental results demonstrated its superior performance in retrieval when it was combined with DDA binary codes.