Structural Prediction of Protein–Protein Interactions by Docking: Application to Biomedical Problems

A huge amount of genetic information is available thanks to the recent advances in sequencing technologies and the larger computational capabilities, but the interpretation of such genetic data at phenotypic level remains elusive. One of the reasons is that proteins are not acting alone, but are specifically interacting with other proteins and biomolecules, forming intricate interaction networks that are essential for the majority of cell processes and pathological conditions. Thus, characterizing such interaction networks is an important step in understanding how information flows from gene to phenotype. Indeed, structural characterization of protein–protein interactions at atomic resolution has many applications in biomedicine, from diagnosis and vaccine design, to drug discovery. However, despite the advances of experimental structural determination, the number of interactions for which there is available structural data is still very small. In this context, a complementary approach is computational modeling of protein interactions by docking, which is usually composed of two major phases: (i) sampling of the possible binding modes between the interacting molecules and (ii) scoring for the identification of the correct orientations. In addition, prediction of interface and hot-spot residues is very useful in order to guide and interpret mutagenesis experiments, as well as to understand functional and mechanistic aspects of the interaction. Computational docking is already being applied to specific biomedical problems within the context of personalized medicine, for instance, helping to interpret pathological mutations involved in protein–protein interactions, or providing modeled structural data for drug discovery targeting protein–protein interactions.Spanish Ministry of Economy grant number BIO2016-79960-R; D.B.B. is supported by a predoctoral fellowship from CONACyT; M.R. is supported by an FPI fellowship from the Severo Ochoa program. We are grateful to the Joint BSC-CRG-IRB Programme in Computational Biology.Peer ReviewedPostprint (author's final draft

A comparative study of breast surface reconstruction for aesthetic outcome assessment

Breast cancer is the most prevalent cancer type in women, and while its survival rate is generally high the aesthetic outcome is an increasingly important factor when evaluating different treatment alternatives. 3D scanning and reconstruction techniques offer a flexible tool for building detailed and accurate 3D breast models that can be used both pre-operatively for surgical planning and post-operatively for aesthetic evaluation. This paper aims at comparing the accuracy of low-cost 3D scanning technologies with the significantly more expensive state-of-the-art 3D commercial scanners in the context of breast 3D reconstruction. We present results from 28 synthetic and clinical RGBD sequences, including 12 unique patients and an anthropomorphic phantom demonstrating the applicability of low-cost RGBD sensors to real clinical cases. Body deformation and homogeneous skin texture pose challenges to the studied reconstruction systems. Although these should be addressed appropriately if higher model quality is warranted, we observe that low-cost sensors are able to obtain valuable reconstructions comparable to the state-of-the-art within an error margin of 3 mm.Comment: This paper has been accepted to MICCAI201

Shape-driven segmentation of the arterial wall in intravascular ultrasound images

Segmentation of arterial wall boundaries from intravascular images is an important problem for many applications in the study of plaque characteristics, mechanical properties of the arterial wall, its 3D reconstruction, and its measurements such as lumen size, lumen radius, and wall radius. We present a shape-driven approach to segmentation of the arterial wall from intravascular ultrasound images in the rectangular domain. In a properly built shape space using training data, we constrain the lumen and media-adventitia contours to a smooth, closed geometry, which increases the segmentation quality without any tradeoff with a regularizer term. In addition to a shape prior, we utilize an intensity prior through a non-parametric probability density based image energy, with global image measurements rather than pointwise measurements used in previous methods. Furthermore, a detection step is included to address the challenges introduced to the segmentation process by side branches and calcifications. All these features greatly enhance our segmentation method. The tests of our algorithm on a large dataset demonstrate the effectiveness of our approach

Constrained estimation of intracranial aneurysm surface deformation using 4D-CTA

Background and objective Intracranial aneurysms are relatively common life-threatening diseases, and assessing aneurysm rupture risk and identifying the associated risk factors is essential. Parameters such as the Oscillatory Shear Index, Pressure Loss Coefficient, and Wall Shear Stress are reliable indicators of intracranial aneurysm development and rupture risk, but aneurysm surface irregular pulsation has also received attention in aneurysm rupture risk assessment. Methods The present paper proposed a new approach to estimate aneurysm surface deformation. This method transforms the estimation of aneurysm surface deformation into a constrained optimization problem, which minimizes the error between the displacement estimated by the model and the sparse data point displacements from the four-dimensional CT angiography (4D-CTA) imaging data. Results The effect of the number of sparse data points on the results has been discussed in both simulation and experimental results, and it shows that the proposed method can accurately estimate the surface deformation of intracranial aneurysms when using sufficient sparse data points. Conclusions Due to a potential association between aneurysm rupture and surface irregular pulsation, the estimation of aneurysm surface deformation is needed. This paper proposed a method based on 4D-CTA imaging data, offering a novel solution for the estimation of intracranial aneurysm surface deformation

2D Reconstruction of Small Intestine's Interior Wall

Examining and interpreting of a large number of wireless endoscopic images from the gastrointestinal tract is a tiresome task for physicians. A practical solution is to automatically construct a two dimensional representation of the gastrointestinal tract for easy inspection. However, little has been done on wireless endoscopic image stitching, let alone systematic investigation. The proposed new wireless endoscopic image stitching method consists of two main steps to improve the accuracy and efficiency of image registration. First, the keypoints are extracted by Principle Component Analysis and Scale Invariant Feature Transform (PCA-SIFT) algorithm and refined with Maximum Likelihood Estimation SAmple Consensus (MLESAC) outlier removal to find the most reliable keypoints. Second, the optimal transformation parameters obtained from first step are fed to the Normalised Mutual Information (NMI) algorithm as an initial solution. With modified Marquardt-Levenberg search strategy in a multiscale framework, the NMI can find the optimal transformation parameters in the shortest time. The proposed methodology has been tested on two different datasets - one with real wireless endoscopic images and another with images obtained from Micro-Ball (a new wireless cubic endoscopy system with six image sensors). The results have demonstrated the accuracy and robustness of the proposed methodology both visually and quantitatively.Comment: Journal draf

Initial results of in vivo non-invasive cancer imaging in the human breast using near-infrared photoacoustics

Near-infrared photoacoustic images of regions-of-interest in 4 of the 5 cases of patients with symptomatic breasts reveal higher intensity regions which we attribute to vascular distribution associated with cancer. Of the 2 cases presented here, one is especially significant where benign indicators dominate in conventional radiological images, while photoacoustic images reveal vascular features suggestive of malignancy, which is corroborated by histopathology. The results show that photoacoustic imaging may have potential in visualizing certain breast cancers based on intrinsic optical absorption contrast. A future role for the approach could be in supplementing conventional breast imaging to assist detection and/or diagnosis.\ud \u