An efficient grid layout algorithm for biological networks utilizing various biological attributes

Background  

Clearly visualized biopathways provide a great help in understanding biological systems. However, manual drawing of large-scale biopathways is time consuming. We proposed a grid layout algorithm that can handle gene-regulatory networks and signal transduction pathways by considering edge-edge crossing, node-edge crossing, distance measure between nodes, and subcellular localization information from Gene Ontology. Consequently, the layout algorithm succeeded in drastically reducing these crossings in the apoptosis model. However, for larger-scale networks, we encountered three problems: (i) the initial layout is often very far from any local optimum because nodes are initially placed at random, (ii) from a biological viewpoint, human layouts still exceed automatic layouts in understanding because except subcellular localization, it does not fully utilize biological information of pathways, and (iii) it employs a local search strategy in which the neighborhood is obtained by moving one node at each step, and automatic layouts suggest that simultaneous movements of multiple nodes are necessary for better layouts, while such extension may face worsening the time complexity.     

Design and validation of surface-marker clusters for the quantification of joint rotations in general movements in early infancy

Lack of complexity in general movements in early infancy is an important marker of potential motor disorders of neurological origin, such as cerebral palsy. Quantitative approaches to characterising this complexity are hampered by experimental difficulties in recording from infants in their first few months of life. The aim of this study was to design and validate bespoke surface-marker clusters to facilitate data acquisition and enable full quantification of joint rotations. The clusters were validated by recording the controlled movements of a soft-body dummy doll simultaneously with an optical (Qualisys) and inertial (XSens) motion capture system. The angles estimated from the optical system were compared with those measured by the inertial system. We demonstrate that the surface-marker based approach compares well with the use of an inertial system to obtain "direct" readings of the rotations whilst alleviating the issues associated with the use of an optical motion capture system. We briefly report use of this technique in 1-5 month old infants. By enabling full quantification of joint rotation, use of the custom made markers could pave the way for early diagnosis of movement disorders.     

Categorizing sex and identity from the biological motion of faces

Head and facial movements can provide valuable cues to identity in addition to their primary roles in communicating speech and expression [1-8]. Here we report experiments in which we have used recent motion capture and animation techniques to animate an average head [9]. These techniques have allowed the isolation of motion from other cues and have enabled us to separate rigid translations and rotations of the head from nonrigid facial motion. In particular, we tested whether human observers can judge sex and identity on the basis of this information. Results show that people can discriminate both between individuals and between males and females from motion-based information alone. Rigid head movements appear particularly useful for categorization on the basis of identity, while nonrigid motion is more useful for categorization on the basis of sex. Accuracy for both sex and identity judgements is reduced when faces are presented upside down, and this finding shows that performance is not based on low-level motion cues alone and suggests that the information is represented in an object-based motion-encoding system specialized for upright faces. Playing animations backward also reduced performance for sex judgements and emphasized the importance of direction specificity in admitting access to stored representations of characteristic male and female movements.     

Optimal Geometrical Set for Automated Marker Placement to Virtualized Real-Time Facial Emotions

In recent years, real-time face recognition has been a major topic of interest in developing intelligent human-machine interaction systems. Over the past several decades, researchers have proposed different algorithms for facial expression recognition, but there has been little focus on detection in real-time scenarios. The present work proposes a new algorithmic method of automated marker placement used to classify six facial expressions: happiness, sadness, anger, fear, disgust, and surprise. Emotional facial expressions were captured using a webcam, while the proposed algorithm placed a set of eight virtual markers on each subject’s face. Facial feature extraction methods, including marker distance (distance between each marker to the center of the face) and change in marker distance (change in distance between the original and new marker positions), were used to extract three statistical features (mean, variance, and root mean square) from the real-time video sequence. The initial position of each marker was subjected to the optical flow algorithm for marker tracking with each emotional facial expression. Finally, the extracted statistical features were mapped into corresponding emotional facial expressions using two simple non-linear classifiers, K-nearest neighbor and probabilistic neural network. The results indicate that the proposed automated marker placement algorithm effectively placed eight virtual markers on each subject’s face and gave a maximum mean emotion classification rate of 96.94% using the probabilistic neural network.     

Effects of damping head movement and facial expression in dyadic conversation using real–time facial expression tracking and synthesized avatars

When people speak with one another, they tend to adapt their head movements and facial expressions in response to each others'' head movements and facial expressions. We present an experiment in which confederates'' head movements and facial expressions were motion tracked during videoconference conversations, an avatar face was reconstructed in real time, and naive participants spoke with the avatar face. No naive participant guessed that the computer generated face was not video. Confederates'' facial expressions, vocal inflections and head movements were attenuated at 1 min intervals in a fully crossed experimental design. Attenuated head movements led to increased head nods and lateral head turns, and attenuated facial expressions led to increased head nodding in both naive participants and confederates. Together, these results are consistent with a hypothesis that the dynamics of head movements in dyadicconversation include a shared equilibrium. Although both conversational partners were blind to the manipulation, when apparent head movement of one conversant was attenuated, both partners responded by increasing the velocity of their head movements.     

Three-dimensional nasolabial displacement during movement in repaired cleft lip and palate patients

The objective of this study was two-fold: (1) to explore the suitability of a novel modified Procrustes fit method to adjust data for head motion during instructed facial movements, and (2) to compare the adjusted data among repaired unilateral (n = 4) and bilateral (n = 5) cleft lip and palate patients and noncleft control subjects (n = 50). Using a video-based tracking system, three-dimensional displacement of 14 well-defined nasolabial landmarks was measured during four set facial animations without controlling for head motion. The modified Procrustes fit method eliminated the contributions of head motion by matching the most stable landmarks of each video-recorded frame of the face during function to frames at rest. Its effectiveness was found to approximate that of a previous method (i.e., use of a maxillary occlusal splint to which stable dentition-based markers were attached). Data from both the unilateral and bilateral cleft lip and palate patients fell outside the normal range of maximum displacements and of asymmetry, and individual patients demonstrated greater right-versus-left asymmetry in maximum displacement than did individual noncleft subjects. It is concluded that the modified Procrustes fit method is fast, is easy to apply, and allows subjects to move the head naturally without the inconvenience of a splint while facial movement data are being collected. Results obtained using this method support the view that facial movements in cleft patients may be severely hampered and that assessment of facial animation should be strongly considered when contemplating surgical lip revisions.     

Non-invasive evaluation of face and motion perception in humans

The neural mechanisms for the perception of face and motion were studied using psychophysical threshold measurements, event-related potentials (ERPs), and functional magnetic resonance imaging (fMRI). A face-specific ERP component, N170, was recorded over the posterior temporal cortex. Removal of the high-spatial-frequency components of the face altered the perception of familiar faces significantly, and familiarity can facilitate the cortico-cortical processing of facial perceptions. Similarly, the high-spatial-frequency components of the face seemed to be crucial for the recognition of facial expressions. Aging and visuospatial impairments affected motion perception significantly. Two distinct components of motion ERPs, N170 and P200, were recorded over the parietal region. The former was related to horizontal motion perception while the latter reflected the perception of radial optic flow motion. The results of fMRI showed that horizontal movements of objects and radial optic flow motion were perceived differently in the V5/MT and superior parietal lobe. We conclude that an integrated approach can provide useful information on spatial and temporal processing of face and motion non-invasively.     

Static accuracy analysis of Vicon T40s motion capture cameras arranged externally for motion capture in constrained aquatic environments

While the capabilities of land-based motion capture systems in biomechanical applications have been previously reported, the possibility of using motion tracking systems externally to reconstruct markers submerged inside an aquatic environment has been under explored. This study assesses the ability of a motion capture system (Vicon T40s) arranged externally to track a retro-reflective marker inside a glass tank filled with water and without water. The reflective tape used for marker creation in this study was of Safety of Life at Sea (SOLAS) grade as the conventional marker loses its reflective properties when submerged. The overall trueness calculated based on the mean marker distance errors, varied between 0.257 mm and 0.290 mm in different mediums (air, glass and water). The overall precision calculated based on mean standard deviation of mean marker distances at different locations varied between 0.046 mm and 0.360 mm in different mediums. Our results suggest, that there is no significant influence of the presence of water on the overall static accuracy of the marker center distances when markers were made of SOLAS grade reflective tape. Using optical motion tracking systems for evaluating locomotion in aquatic environment can help to better understand the effects of aquatic therapy in clinical rehabilitation, especially in scenarios that involve equipment, such as an underwater treadmill which generally have constrained capture volumes for motion capture.     

Quantifying facial asymmetry. A method for objective assessment of impairments of facial motoricity; a pilot study]

The aim of this study was to develop a method of objectively evaluating the results of a dynamic reconstruction of facial nerve paralysis by means of nerve transplants with a view to reinnervating a free muscle transplant. The Vicon 3 D motion analysis system was used to measure the distances and movements of marker points on the face of the patient. This objective technique permits evaluation of the operation as well as the results of treatment.     

The Marking Technology in Motion Capture for the Complex Locomotor Behavior of Flexible Small Animals(Gekko gecko)

Animals have evolved a variety of behavior patterns to adapt to the environment. Motion-capture technology is utilized to quantify and characterize locomotor behaviors to reveal the mechanisms of animal motion. In the capture of flexible, small animals with complex locomotor behaviors, the markers interfere with each other easily, and the motion forms(bending, twisting) of the moving parts are obviously different; thus, it is a great challenge to realize accurate quantitative characterization of complex locomotor behaviors. The correlation between the marker properties, including the size and space length, and the precision of the system are revealed in this paper, and the effects of diverse marker shapes on the capturing accuracy of the captured objects in different motion forms were tested. Results showed that the precision of system is significantly improved when the ratio of the space length to the diameter of the markers is larger than four; for the capture of the spatial twisting motion of the flexible object, the hexagon markers had the lowest spatial lost-marker rate relative to the circle, triangle, and square. Customized markers were used to capture the locomotor behavior of the gecko-inspired robot(rigid connection) and the gecko(flexible connection). The results showed that this marking technology can achieve high accuracy of motion capture for geckos(the average deviation was approximately 0.32 mm, and the average deviation's variation rate was approximately 0.96%). In this paper, the marking technology for the motion capture of flexible, small animals with complex motion is proposed; it can effectively improve the system precision as well as the capture accuracy, and realize the quantitative characterization of the complex motion of flexible, small objects. It provides a reliable technical means to deeply study the evolution of the motion function of small animals and advance systematic research of motion-capture technology.     

Segmental motion of forefoot and hindfoot as a diagnostic tool

Segmental motions derived from non-invasive motion analysis are being used to investigate the intrinsic functional behavior of the foot and ankle in health and disease. The goal of this research was to examine the ability of a generic segmented model of the foot to capture and differentiate changes in internal skeletal kinematics due to neuromuscular disease and/or trauma. A robotic apparatus that reproduces the kinematics and kinetics of gait in cadaver lower extremities was employed to produce motion under normal and aberrant neuromuscular activation patterns of tibialis posterior and/or tibialis anterior. Stance phase simulations were conducted on 10 donor limbs while recording three-dimensional kinematic trajectories of (1) skin-mounted markers used clinically to construct segmented foot models, and (2) bone-mounted marker clusters to capture actual internal bone motion as the gold standard for comparison. The models constructed from external marker data were able to differentiate the kinematic behaviors elicited by different neuromuscular conditions in a manner similar to that using the bone-derived data. Measurable differences between internal and externally measured kinematics were small, variable and random across the three axes of rotation and neuromuscular conditions, with a tendency toward more differences noted during early and late stance. Albeit slightly different, three-dimensional motion profiles of the hindfoot and forefoot segments correlated well with internal skeletal motion under all neuromuscular conditions, thereby confirming the utility of measuring segmental motions as a valid means of clinical assessment.     

Anatomy of emotion: a 3D study of facial mimicry

Alterations in facial motion severely impair the quality of life and social interaction of patients, and an objective grading of facial function is necessary. A method for the non-invasive detection of 3D facial movements was developed. Sequences of six standardized facial movements (maximum smile; free smile; surprise with closed mouth; surprise with open mouth; right side eye closure; left side eye closure) were recorded in 20 healthy young adults (10 men, 10 women) using an optoelectronic motion analyzer. For each subject, 21 cutaneous landmarks were identified by 2-mm reflective markers, and their 3D movements during each facial animation were computed. Three repetitions of each expression were recorded (within-session error), and four separate sessions were used (between-session error). To assess the within-session error, the technical error of the measurement (random error, TEM) was computed separately for each sex, movement and landmark. To assess the between-session repeatability, the standard deviation among the mean displacements of each landmark (four independent sessions) was computed for each movement. TEM for the single landmarks ranged between 0.3 and 9.42 mm (intrasession error). The sex- and movement-related differences were statistically significant (two-way analysis of variance, p=0.003 for sex comparison, p=0.009 for the six movements, p<0.001 for the sex x movement interaction). Among four different (independent) sessions, the left eye closure had the worst repeatability, the right eye closure had the best one; the differences among various movements were statistically significant (one-way analysis of variance, p=0.041). In conclusion, the current protocol demonstrated a sufficient repeatability for a future clinical application. Great care should be taken to assure a consistent marker positioning in all the subjects.     

Direct comparison of kinematic data collected using an electromagnetic tracking system versus a digital optical system

The purpose of this study was to quantify the dynamic accuracy of kinematics measured by a digital optical motion analysis system in a gait analysis laboratory (capture volume approximately 20m(3)) compared to a standard range direct-current electromagnetic (EM) tracking device (capture volume approximately 1m(3)). This is a subset of a larger effort to establish an appropriate marker set for the optical system to quantify upperlimb kinematics simultaneously with gait, in comparison to previous studies of isolated upperlimb movements that have employed EM tracking devices. Rigid clusters of spherical reflective markers and EM sensors were attached to a mechanical articulator that mimicked three-dimensional joint rotations, similar to the elbow. As the articulator was moved through known ranges of motion (i.e. gold standard), kinematic data were collected simultaneously using both tracking systems. Both systems were tended to underestimate the range of motion; however, the application of post hoc smoothing and least-squares correction algorithms reduced these effects. When smoothing and correction algorithms were used, the magnitude of the mean difference between the gold standard and either the EM or optical system did not exceed 2 degrees for any of the compound motions performed. This level of agreement suggests that the measurements obtained from either system are clinically comparable, provided appropriate smoothing and correction algorithms are employed.     

Kinematical models to reduce the effect of skin artifacts on marker-based human motion estimation

The estimation of the skeletal motion obtained from marker-based motion capture systems is known to be affected by significant bias caused by skin movement artifacts, which affects joint center and rotation axis estimation. Among different techniques proposed in the literature, that based on rigid body model, still the most used by commercial motion capture systems, can smooth only part of the above effects without eliminating their main components. In order to sensibly improve the accuracy of the motion estimation, a novel technique, named local motion estimation (LME), is proposed. This rests on a recently described approach that, using virtual humans and extended Kalman filters, estimates the kinematical variables directly from 2D measurements without requiring the 3D marker reconstruction. In this paper, we show how such method can be extended to include the computation of the local marker displacement due to skin artifacts. The 3D marker coordinates, expressed in the corresponding local reference coordinate frames, are inserted into the state vector of the filter and their dynamics is automatically estimated, with adequate accuracy, without assuming any particular deformation function. Simulated experiments of lower limb motion, involving systematic mislocations (5, 10, 20 mm) and random errors of the marker coordinates and joint center locations (+/-5, +/-10, +/-15 mm), have shown that artifact motion can be substantially decoupled from the global skeletal motion with an effective increase of the accuracy wrt standard techniques. In particular, the comparison between the nominal kinematical variables and the one recovered from markers attached to the skin surface proved LME to be sensibly superior (50% in the worse condition) to the methods imposing marker-bone rigidity. In conclusion, while requiring further validation on real movement data, we argue that the proposed method can constitute an appropriate approach toward the improvement of the human motion estimation.     

Accuracy map of an optical motion capture system with 42 or 21 cameras in a large measurement volume

Optical motion capture is commonly used in biomechanics to measure human kinematics. However, no studies have yet examined the accuracy of optical motion capture in a large capture volume (>100 m³), or how accuracy varies from the center to the extreme edges of the capture volume. This study measured the dynamic 3D errors of an optical motion capture system composed of 42 OptiTrack Prime 41 cameras (capture volume of 135 m³) by comparing the motion of a single marker to the motion reported by a ThorLabs linear motion stage. After spline interpolating the data, it was found that 97% of the capture area had error below 200 μm. When the same analysis was performed using only half (21) of the cameras, 91% of the capture area was below 200 μm of error. The only locations that exceeded this threshold were at the extreme edges of the capture area, and no location had a mean error exceeding 1 mm. When measuring human kinematics with skin-mounted markers, uncertainty of marker placement relative to underlying skeletal features and soft tissue artifact produce errors that are orders of magnitude larger than the errors attributed to the camera system itself. Therefore, the accuracy of this OptiTrack optical motion capture system was found to be more than sufficient for measuring full-body human kinematics with skin-mounted markers in a large capture volume (>100 m³).     

Robust approach to combining multiple markers to improve surrogacy

Identifying effective and valid surrogate markers to make inference about a treatment effect on long-term outcomes is an important step in improving the efficiency of clinical trials. Replacing a long-term outcome with short-term and/or cheaper surrogate markers can potentially shorten study duration and reduce trial costs. There is sizable statistical literature on methods to quantify the effectiveness of a single surrogate marker. Both parametric and nonparametric approaches have been well developed for different outcome types. However, when there are multiple markers available, methods for combining markers to construct a composite marker with improved surrogacy remain limited. In this paper, building on top of the optimal transformation framework of Wang et al. (2020), we propose a novel calibrated model fusion approach to optimally combine multiple markers to improve surrogacy. Specifically, we obtain two initial estimates of optimal composite scores of the markers based on two sets of models with one set approximating the underlying data distribution and the other directly approximating the optimal transformation function. We then estimate an optimal calibrated combination of the two estimated scores which ensures both validity of the final combined score and optimality with respect to the proportion of treatment effect explained by the final combined score. This approach is unique in that it identifies an optimal combination of the multiple surrogates without strictly relying on parametric assumptions while borrowing modeling strategies to avoid fully nonparametric estimation which is subject to the curse of dimensionality. Our identified optimal transformation can also be used to directly quantify the surrogacy of this identified combined score. Theoretical properties of the proposed estimators are derived, and the finite sample performance of the proposed method is evaluated through simulation studies. We further illustrate the proposed method using data from the Diabetes Prevention Program study.     

Automated tracking of facial features in patients with facial neuromuscular dysfunction

Facial neuromuscular dysfunction severely impacts adaptive and expressive behavior and emotional health. Appropriate treatment is aided by quantitative and efficient assessment of facial motion impairment. We validated a newly developed method of quantifying facial motion, automated face analysis (AFA), by comparing it with an established manual marking method, the Maximal Static Response Assay (MSRA). In the AFA, motion of facial features is tracked automatically by computer vision without the need for placement of physical markers or restrictions of rigid head motion. Nine patients (seven women and two men) with a mean age of 39.3 years and various facial nerve disorders (five with Bell's palsy, three with trauma, and one with tumor resection) participated. The patients were videotaped while performing voluntary facial action tasks (brow raise, eye closure, and smile). For comparison with MSRA, physical markers were placed on facial landmarks. Image sequences were digitized into 640 x 480 x 24-bit pixel arrays at 30 frames per second (1 pixel congruent with0.3 mm). As defined for the MSRA, the coordinates of the center of each marker were manually recorded in the initial and final digitized frames, which correspond to repose and maximal response. For the AFA, these points were tracked automatically in the image sequence. Pearson correlation coefficients were used to evaluate consistency of measurement between manual (the MSRA) and automated (the AFA) tracking methods, and paired t tests were used to assess the mean difference between methods for feature tracking. Feature measures were highly consistent between methods, Pearson's r = 0.96 or higher, p < 0.001 for each of the action tasks. The mean differences between the methods were small; the mean error between methods was comparable to the error within the manual method (less than 1 pixel). The AFA demonstrated strong concurrent validity with the MSRA for pixel-wise displacement. Tracking was fully automated and provided motion vectors, which may be useful in guiding surgical and rehabilitative approaches to restoring facial function in patients with facial neuromuscular disorders.     

An ultrasound based non-invasive method for the measurement of intrinsic foot kinematics during gait

Soft tissue artefact (STA) and marker placement variability are sources of error when measuring the intrinsic kinematics of the foot. This study aims to demonstrate a non-invasive, combined ultrasound and motion capture (US/MC) technique to directly measure foot skeletal motion. The novel approach is compared to a standard motion capture protocol. Fourteen participants underwent instrumented barefoot analysis of foot motion during gait. Markers were attached to foot allowing medial longitudinal arch angle and navicular height to be determined. For the US/MC technique, the navicular marker was replaced by an ultrasound transducer which was secured to the foot allowing the skeletal landmark to be imaged. Ultrasound cineloops showing the location of the navicular tuberosity during the walking trials were synchronised with motion capture measurements and markers mounted on the probe allowed the true position of the bony landmark to be determined throughout stance phase. Two discrete variables, minimum navicular height and maximum MLA angle, were compared between the standard and US/MC protocols. Significant differences between minimum navicular height (P=0.004, 95% CI (1.57, 6.54)) and maximum medial longitudinal arch angle (P=0.0034, 95% CI (13.8, 3.4)) were found between the measurement methods. The individual effects of STA and marker placement error were also assessed. US/MC is a non-invasive technique which may help to provide more accurate measurements of intrinsic foot kinematics.     

Hypoglossal-facial nerve anastomosis for reinnervation of the paralyzed face.

The hypoglossal-facial nerve crossover is a valuable surgical procedure for the treatment of certain types of facial paralysis. It is most effective when used as an integral part of a primary ablative operation for the treatment of cancer in this region. In the treatment of long-standing facial paralysis, its application requires an intact peripheral facial nerve system and some functioning mimetic muscles with an obliterated proximal facial nerve segment. It is recognized that other procedures are available for repair in patients who meet essentially these same criteria. The disadvantages are minimal intraoral crippling, mass movements of the face and, in some instances, hypertonia of the face. The advantages are improved facial tone, protection of the eye, intentional facial movements controlled by the tongue, and movements associated with physiological functions of the tongue.     

Three-dimensional video analysis of facial movements: a new method to assess the quantity and quality of the smile

The results of neuromuscular reconstructions of the paralyzed face are difficult to assess. Very sophisticated methods are necessary to measure the motor deficits of facial paralysis or the functional recovery in the face. The aim of this development was a relatively simple system for data acquisition, which is easy to handle and which makes it relatively cheap to delegate data acquisition to centers all over the world, which will not be able to derive a data analysis on their own, but will send their data to a center with specialized equipment. A complex mirror system was developed to get three different views of the face at the same time on the video screen. At each investigation, a digital video is taken from a calibration grid and from standardized facial movements of the patient. Secondary analysis of the digital videofilm is made possible at any time later on by the support of a computer program, which calculates distances and movements three-dimensionally from the frontal image and the right and left mirror images. Pathologies of the mimic movements can be identified as well as improvements after surgical procedures by this system. The significant advantage is the possibility to watch the same movement on the video which is under study and to apply any kind of study later on. Taking the video needs only a few minutes, and fatigue of the patient's mimic system is prevented. Measurements usually at the endpoints of the movements give excellent information on the quantity of the movement or the degree of the facial palsy, whereas the video itself is very informative regarding the quality of the smile. Specific computer software was developed for standardized three-dimensional analysis of the video-documented facial movements and for data presentation. There are options like two-dimensional graphs of single moving points in the face or three-dimensional graphs of the movements of all measured points at the same time during a standardized facial movement. By a comparison of the right- and left-sided alterations of specific distances between two points during the facial movements, the degree of normal symmetry or pathologic asymmetry is quantified. This system is more suitable for detailed scientific multicenter studies than any other system previously established. A very sensitive instrument for exact evaluation of mimic function is now available.