On the reliability of single-camera markerless systems for overground gait monitoring.

BACKGROUND AND OBJECTIVE: Motion analysis is crucial for effective and timely rehabilitative interventions on people with motor disorders. Conventional marker-based (MB) gait analysis is highly time-consuming and calls for expensive equipment, dedicated facilities and personnel. Markerless (ML) systems may pave the way to less demanding gait monitoring, also in unsupervised environments (i.e., in telemedicine). However,scepticism on clinical usability of relevant outcome measures has hampered its use. ML is normally used to analyse treadmill walking, which is significantly different from the more physiological overground walking. This study aims to provide end-users with instructions on using a single-camera markerless system to obtain reliable motion data from overground walking, while clinicians will be instructed on the reliability of obtained quantities. METHODS: The study compares kinematics obtained from ML systems to those concurrently obtained from marker-based systems, considering different stride counts and subject positioning within the capture volume. RESULTS: The findings suggest that five straight walking trials are sufficient for collecting reliable kinematics with ML systems. Precision on joint kinematics decreased at the boundary of the capture volume. Excellent correlation was found between ML and MB systems for hip and knee angles (0.92

Assessment of Axial Postural Abnormalities in Parkinsonism: Automatic Picture Analysis Software.

Background: Software-based measurements of axial postural abnormalities in Parkinson's disease (PD) are the gold standard but may be time-consuming and not always feasible in clinical practice. An automatic and reliable software to accurately obtain real-time spine flexion angles according to the recently proposed consensus-based criteria would be a useful tool for both research and clinical practice. Objective: We aimed to develop and validate a new software based on Deep Neural Networks to perform automatic measures of PD axial postural abnormalities. Methods: A total of 76 pictures from 55 PD patients with different degrees of anterior and lateral trunk flexion were used for the development and pilot validation of a new software called AutoPosturePD (APP); postural abnormalities were measured in lateral and posterior view using the freeware NeuroPostureApp (gold standard) and compared with the automatic measurement provided by the APP. Sensitivity and specificity for the diagnosis of camptocormia and Pisa syndrome were assessed. Results: We found an excellent agreement between the new APP and the gold standard for lateral trunk flexion (intraclass correlation coefficient [ICC] 0.960, IC95% 0.913-0.982, P < 0.001), anterior trunk flexion with thoracic fulcrum (ICC 0.929, IC95% 0.846-0.968, P < 0.001) and anterior trunk flexion with lumbar fulcrum (ICC 0.991, IC95% 0.962-0.997, P < 0.001). Sensitivity and specificity were 100% and 100% for detecting Pisa syndrome, 100% and 95.5% for camptocormia with thoracic fulcrum, 100% and 80.9% for camptocormia with lumbar fulcrum. Conclusions: AutoPosturePD is a valid tool for spine flexion measurement in PD, accurately supporting the diagnosis of Pisa syndrome and camptocormia.

Camera- and Viewpoint-Agnostic Evaluation of Axial Postural Abnormalities in People with Parkinson's Disease through Augmented Human Pose Estimation.

Axial postural abnormalities (aPA) are common features of Parkinson's disease (PD) and manifest in over 20% of patients during the course of the disease. aPA form a spectrum of functional trunk misalignment, ranging from a typical Parkinsonian stooped posture to progressively greater degrees of spine deviation. Current research has not yet led to a sufficient understanding of pathophysiology and management of aPA in PD, partially due to lack of agreement on validated, user-friendly, automatic tools for measuring and analysing the differences in the degree of aPA, according to patients' therapeutic conditions and tasks. In this context, human pose estimation (HPE) software based on deep learning could be a valid support as it automatically extrapolates spatial coordinates of the human skeleton keypoints from images or videos. Nevertheless, standard HPE platforms have two limitations that prevent their adoption in such a clinical practice. First, standard HPE keypoints are inconsistent with the keypoints needed to assess aPA (degrees and fulcrum). Second, aPA assessment either requires advanced RGB-D sensors or, when based on the processing of RGB images, they are most likely sensitive to the adopted camera and to the scene (e.g., sensor-subject distance, lighting, background-subject clothing contrast). This article presents a software that augments the human skeleton extrapolated by state-of-the-art HPE software from RGB pictures with exact bone points for posture evaluation through computer vision post-processing primitives. This article shows the software robustness and accuracy on the processing of 76 RGB images with different resolutions and sensor-subject distances from 55 PD patients with different degrees of anterior and lateral trunk flexion.

Human genetic diversity alters off-target outcomes of therapeutic gene editing.

CRISPR gene editing holds great promise to modify DNA sequences in somatic cells to treat disease. However, standard computational and biochemical methods to predict off-target potential focus on reference genomes. We developed an efficient tool called CRISPRme that considers single-nucleotide polymorphism (SNP) and indel genetic variants to nominate and prioritize off-target sites. We tested the software with a BCL11A enhancer targeting guide RNA (gRNA) showing promise in clinical trials for sickle cell disease and ß-thalassemia and found that the top candidate off-target is produced by an allele common in African-ancestry populations (MAF 4.5%) that introduces a protospacer adjacent motif (PAM) sequence. We validated that SpCas9 generates strictly allele-specific indels and pericentric inversions in CD34+ hematopoietic stem and progenitor cells (HSPCs), although high-fidelity Cas9 mitigates this off-target. This report illustrates how genetic variants should be considered as modifiers of gene editing outcomes. We expect that variant-aware off-target assessment will become integral to therapeutic genome editing evaluation and provide a powerful approach for comprehensive off-target nomination.

Preserving Data Privacy and Accuracy of Human Pose Estimation Software Based on CNN s for Remote Gait Analysis.

In the last years there have been significant improvements in the accuracy of real-time 3D skeletal data estimation software. These applications based on convolutional neural networks (CNNs) can playa key role in a variety of clinical scenarios, from gait analysis to medical diagnosis. One of the main challenges is to apply such intelligent video analytic at a distance, which requires the system to satisfy, beside accuracy, also data privacy. To satisfy privacy by default and by design, the software has to run on "edge" computing devices, by which the sensitive information (i.e., the video stream) is elaborated close to the camera while only the process results can be stored or sent over the communication network. In this paper we address such a challenge by evaluating the accuracy of the state-of-the-art software for human pose estimation when run "at the edge". We show how the most accurate platforms for pose estimation based on complex and deep neural networks can become inaccurate due to subs amp ling of the input video frames when run on the resource constrained edge devices. In contrast, we show that, starting from less accurate and "lighter" CNNs and enhancing the pose estimation software with filters and interpolation primitives, the platform achieves better real-time performance and higher accuracy with a deviation below the error tolerance of a marker-based motion capture system.

Enabling Gait Analysis in the Telemedicine Practice through Portable and Accurate 3D Human Pose Estimation.

Human pose estimation (HPE) through deep learning-based software applications is a trend topic for markerless motion analysis. Thanks to the accuracy of the state-of-the-art technology, HPE could enable gait analysis in the telemedicine practice. On the other hand, delivering such a service at a distance requires the system to satisfy multiple and different constraints like accuracy, portability, real-time, and privacy compliance at the same time. Existing solutions either guarantee accuracy and real-time (e.g., the widespread OpenPose software on well-equipped computing platforms) or portability and data privacy (e.g., light convolutional neural networks on mobile phones). We propose a portable and low-cost platform that implements real-time and accurate 3D HPE through an embedded software on a low-power off-the-shelf computing device that guarantees privacy by default and by design. We present an extended evaluation of both accuracy and performance of the proposed solution conducted with a marker-based motion capture system (i.e., Vicon) as ground truth. The results show that the platform achieves real-time performance and high-accuracy with a deviation below the error tolerance when compared to the marker-based motion capture system (e.g., less than an error of 5∘ on the estimated knee flexion difference on the entire gait cycle and correlation 0.91<ρ<0.99). We provide a proof-of-concept study, showing that such portable technology, considering the limited discrepancies with respect to the marker-based motion capture system and its working tolerance, could be used for gait analysis at a distance without leading to different clinical interpretation.

Efficient implementation of the Shack-Hartmann centroid extraction for edge computing.

Adaptive optics (AO) is an established technique to measure and compensate for optical aberrations. One of its key components is the wavefront sensor (WFS), which is typically a Shack-Hartmann sensor (SH) capturing an image related to the aberrated wavefront. We propose an efficient implementation of the SH-WFS centroid extraction algorithm, tailored for edge computing. In the edge-computing paradigm, the data are elaborated close to the source (i.e., at the edge) through low-power embedded architectures, in which CPU computing elements are combined with heterogeneous accelerators (e.g., GPUs, field-programmable gate arrays). Since the control loop latency must be minimized to compensate for the wavefront aberration temporal dynamics, we propose an optimized algorithm that takes advantage of the unified CPU/GPU memory of recent low-power embedded architectures. Experimental results show that the centroid extraction latency obtained over spot images up to 700×700 pixels wide is smaller than 2 ms. Therefore, our approach meets the temporal requirements of small- to medium-sized AO systems, which are equipped with deformable mirrors having tens of actuators.

CRISPRitz: rapid, high-throughput and variant-aware in silico off-target site identification for CRISPR genome editing.

MOTIVATION: Clustered regularly interspaced short palindromic repeats (CRISPR) technologies allow for facile genomic modification in a site-specific manner. A key step in this process is the in silico design of single guide RNAs to efficiently and specifically target a site of interest. To this end, it is necessary to enumerate all potential off-target sites within a given genome that could be inadvertently altered by nuclease-mediated cleavage. Currently available software for this task is limited by computational efficiency, variant support or annotation, and assessment of the functional impact of potential off-target effects. RESULTS: To overcome these limitations, we have developed CRISPRitz, a suite of software tools to support the design and analysis of CRISPR/CRISPR-associated (Cas) experiments. Using efficient data structures combined with parallel computation, we offer a rapid, reliable, and exhaustive search mechanism to enumerate a comprehensive list of putative off-target sites. As proof-of-principle, we performed a head-to-head comparison with other available tools on several datasets. This analysis highlighted the unique features and superior computational performance of CRISPRitz including support for genomic searching with DNA/RNA bulges and mismatches of arbitrary size as specified by the user as well as consideration of genetic variants (variant-aware). In addition, graphical reports are offered for coding and non-coding regions that annotate the potential impact of putative off-target sites that lie within regions of functional genomic annotation (e.g. insulator and chromatin accessible sites from the ENCyclopedia Of DNA Elements [ENCODE] project). AVAILABILITY AND IMPLEMENTATION: The software is freely available at: https://github.com/pinellolab/CRISPRitzhttps://github.com/InfOmics/CRISPRitz. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Correction to: cuRnet: an R package for graph traversing on GPU.

After publication of this supplement article [1], it was brought to our attention that reference 10 and reference 12 in the article are incorrect.

cuRnet: an R package for graph traversing on GPU.

BACKGROUND: R has become the de-facto reference analysis environment in Bioinformatics. Plenty of tools are available as packages that extend the R functionality, and many of them target the analysis of biological networks. Several algorithms for graphs, which are the most adopted mathematical representation of networks, are well-known examples of applications that require high-performance computing, and for which classic sequential implementations are becoming inappropriate. In this context, parallel approaches targeting GPU architectures are becoming pervasive to deal with the execution time constraints. Although R packages for parallel execution on GPUs are already available, none of them provides graph algorithms. RESULTS: This work presents cuRnet, a R package that provides a parallel implementation for GPUs of the breath-first search (BFS), the single-source shortest paths (SSSP), and the strongly connected components (SCC) algorithms. The package allows offloading computing intensive applications to GPU devices for massively parallel computation and to speed up the runtime up to one order of magnitude with respect to the standard sequential computations on CPU. We have tested cuRnet on a benchmark of large protein interaction networks and for the interpretation of high-throughput omics data thought network analysis. CONCLUSIONS: cuRnet is a R package to speed up graph traversal and analysis through parallel computation on GPUs. We show the efficiency of cuRnet applied both to biological network analysis, which requires basic graph algorithms, and to complex existing procedures built upon such algorithms.

Arena-Idb: a platform to build human non-coding RNA interaction networks.

BACKGROUND: High throughput technologies have provided the scientific community an unprecedented opportunity for large-scale analysis of genomes. Non-coding RNAs (ncRNAs), for a long time believed to be non-functional, are emerging as one of the most important and large family of gene regulators and key elements for genome maintenance. Functional studies have been able to assign to ncRNAs a wide spectrum of functions in primary biological processes, and for this reason they are assuming a growing importance as a potential new family of cancer therapeutic targets. Nevertheless, the number of functionally characterized ncRNAs is still too poor if compared to the number of new discovered ncRNAs. Thus platforms able to merge information from available resources addressing data integration issues are necessary and still insufficient to elucidate ncRNAs biological roles. RESULTS: In this paper, we describe a platform called Arena-Idb for the retrieval of comprehensive and non-redundant annotated ncRNAs interactions. Arena-Idb provides a framework for network reconstruction of ncRNA heterogeneous interactions (i.e., with other type of molecules) and relationships with human diseases which guide the integration of data, extracted from different sources, via mapping of entities and minimization of ambiguity. CONCLUSIONS: Arena-Idb provides a schema and a visualization system to integrate ncRNA interactions that assists in discovering ncRNA functions through the extraction of heterogeneous interaction networks. The Arena-Idb is available at http://arenaidb.ba.itb.cnr.it.

MIRATE: MIps RATional dEsign Science Gateway.

Molecularly imprinted polymers (MIPs) are high affinity robust synthetic receptors, which can be optimally synthesized and manufactured more economically than their biological equivalents (i.e. antibody). In MIPs production, rational design based on molecular modeling is a commonly employed technique. This mostly aids in (i) virtual screening of functional monomers (FMs), (ii) optimization of monomer-template ratio, and (iii) selectivity analysis. We present MIRATE, an integrated science gateway for the intelligent design of MIPs. By combining and adapting multiple state-of-the-art bioinformatics tools into automated and innovative pipelines, MIRATE guides the user through the entire process of MIPs' design. The platform allows the user to fully customize each stage involved in the MIPs' design, with the main goal to support the synthesis in the wet-laboratory. Availability: MIRATE is freely accessible with no login requirement at http://mirate.di.univr.it/. All major browsers are supported.

An Efficient Approach for Accelerating Bucket Elimination on GPUs.

Bucket elimination (BE) is a framework that encompasses several algorithms, including belief propagation (BP) and variable elimination for constraint optimization problems (COPs). BE has significant computational requirements that can be addressed by using graphics processing units (GPUs) to parallelize its fundamental operations, i.e., composition and marginalization, which operate on functions represented by large tables. We propose a novel approach to parallelize these operations with GPUs, which optimizes the table layout so to achieve better performance in terms of increased speedup and scalability. Our approach allows us to process incomplete tables (i.e., tables with some missing variables assignments), which often occur in several practical applications (such as the ones we consider in our dataset). Finally, we can process tables that are larger than the GPU memory. Our approach outperforms the state-of-the-art technique to parallelize BP on GPUs, achieving better speedups (up to +466% with respect to such parallel technique). We test our method on a publicly available COP dataset, measuring a speedup up to with respect to the sequential version. The ability of our technique to process large tables is crucial in this scenario, in which most of the instances generate tables larger than the GPU memory, and hence they cannot be solved with previous GPU techniques related to BE.

APPAGATO: an APproximate PArallel and stochastic GrAph querying TOol for biological networks.

MOTIVATION: Biological network querying is a problem requiring a considerable computational effort to be solved. Given a target and a query network, it aims to find occurrences of the query in the target by considering topological and node similarities (i.e. mismatches between nodes, edges, or node labels). Querying tools that deal with similarities are crucial in biological network analysis because they provide meaningful results also in case of noisy data. In addition, as the size of available networks increases steadily, existing algorithms and tools are becoming unsuitable. This is rising new challenges for the design of more efficient and accurate solutions. RESULTS: This paper presents APPAGATO, a stochastic and parallel algorithm to find approximate occurrences of a query network in biological networks. APPAGATO handles node, edge and node label mismatches. Thanks to its randomic and parallel nature, it applies to large networks and, compared with existing tools, it provides higher performance as well as statistically significant more accurate results. Tests have been performed on protein-protein interaction networks annotated with synthetic and real gene ontology terms. Case studies have been done by querying protein complexes among different species and tissues. AVAILABILITY AND IMPLEMENTATION: APPAGATO has been developed on top of CUDA-C ++ Toolkit 7.0 framework. The software is available online http://profs.sci.univr.it/∼bombieri/APPAGATO CONTACT: rosalba.giugno@univr.it SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Comprehensive reconstruction and visualization of non-coding regulatory networks in human.

Research attention has been powered to understand the functional roles of non-coding RNAs (ncRNAs). Many studies have demonstrated their deregulation in cancer and other human disorders. ncRNAs are also present in extracellular human body fluids such as serum and plasma, giving them a great potential as non-invasive biomarkers. However, non-coding RNAs have been relatively recently discovered and a comprehensive database including all of them is still missing. Reconstructing and visualizing the network of ncRNAs interactions are important steps to understand their regulatory mechanism in complex systems. This work presents ncRNA-DB, a NoSQL database that integrates ncRNAs data interactions from a large number of well established on-line repositories. The interactions involve RNA, DNA, proteins, and diseases. ncRNA-DB is available at http://ncrnadb.scienze.univr.it/ncrnadb/. It is equipped with three interfaces: web based, command-line, and a Cytoscape app called ncINetView. By accessing only one resource, users can search for ncRNAs and their interactions, build a network annotated with all known ncRNAs and associated diseases, and use all visual and mining features available in Cytoscape.

GRAPES: a software for parallel searching on biological graphs targeting multi-core architectures.

Biological applications, from genomics to ecology, deal with graphs that represents the structure of interactions. Analyzing such data requires searching for subgraphs in collections of graphs. This task is computationally expensive. Even though multicore architectures, from commodity computers to more advanced symmetric multiprocessing (SMP), offer scalable computing power, currently published software implementations for indexing and graph matching are fundamentally sequential. As a consequence, such software implementations (i) do not fully exploit available parallel computing power and (ii) they do not scale with respect to the size of graphs in the database. We present GRAPES, software for parallel searching on databases of large biological graphs. GRAPES implements a parallel version of well-established graph searching algorithms, and introduces new strategies which naturally lead to a faster parallel searching system especially for large graphs. GRAPES decomposes graphs into subcomponents that can be efficiently searched in parallel. We show the performance of GRAPES on representative biological datasets containing antiviral chemical compounds, DNA, RNA, proteins, protein contact maps and protein interactions networks.