Automated annotation of protein function is challenging. As the number of sequenced genomes rapidly grows, the overwhelming majority of protein products can only be annotated computationally. If computational predictions are to be relied upon, it is crucial that the accuracy of these methods be high. Here we report the results from the first large-scale community-based Critical Assessment of protein Function Annotation (CAFA) experiment. Fifty-four methods representing the state-of-the-art for protein function prediction were evaluated on a target set of 866 proteins from eleven organisms. Two findings stand out: (i) today’s best protein function prediction algorithms significantly outperformed widely-used first-generation methods, with large gains on all types of targets; and (ii) although the top methods perform well enough to guide experiments, there is significant need for improvement of currently available tools.

Endothelial to mesenchymal transition (EndMT) plays a major role during development, and also contributes to several adult cardiovascular diseases. Importantly, mesenchymal cells including fibroblasts are prominent in atherosclerosis, with key functions including regulation of: inflammation, matrix and collagen production, and plaque structural integrity. However, little is known about the origins of atherosclerosis-associated fibroblasts. Here we show using endothelial-specific lineage-tracking that EndMT-derived fibroblast-like cells are common in atherosclerotic lesions, with EndMT-derived cells expressing a range of fibroblast-specific markers. In vitro modelling confirms that EndMT is driven by TGF-β signalling, oxidative stress and hypoxia; all hallmarks of atherosclerosis. ‘Transitioning' cells are readily detected in human plaques co-expressing endothelial and fibroblast/mesenchymal proteins, indicative of EndMT. The extent of EndMT correlates with an unstable plaque phenotype, which appears driven by altered collagen-MMP production in EndMT-derived cells. We conclude that EndMT contributes to atherosclerotic patho-biology and is associated with complex plaques that may be related to clinical events.

This paper reports on an algorithm for automatic, targetless, extrinsic calibration of a lidar and optical camera system based upon the maximization of mutual information between the sensor-measured surface intensities. The proposed method is completely data-driven and does not require any fiducial calibration targets-making in situ calibration easy. We calculate the Cramér-Rao lower bound (CRLB) of the estimated calibration parameter variance, and we show experimentally that the sample variance of the estimated parameters empirically approaches the CRLB when the amount of data used for calibration is sufficiently large. Furthermore, we compare the calibration results to independent ground-truth (where available) and observe that the mean error empirically approaches zero as the amount of data used for calibration is increased, thereby suggesting that the proposed estimator is a minimum variance unbiased estimate of the calibration parameters. Experimental results are presented for three different lidar-camera systems: (i) a three-dimensional (3D) lidar and omnidirectional camera, (ii) a 3D time-of-flight sensor and monocular camera, and (iii) a 2D lidar and monocular camera. C

Abstract

Autonomous vehicles require precise knowledge of their position and orientation in all weather and traffic conditions for path planning, perception, control, and general safe operation. Here we derive these requirements for autonomous vehicles based on first principles. We begin with the safety integrity level, defining the allowable probability of failure per hour of operation based on desired improvements on road safety today. This draws comparisons with the localization integrity levels required in aviation and rail where similar numbers are derived at 10 -8 probability of failure per hour of operation. We then define the geometry of the problem, where the aim is to maintain knowledge that the vehicle is within its lane and to determine what road level it is on. Longitudinal, lateral, and vertical localization error bounds (alert limits) and 95% accuracy requirements are derived based on US road geometry standards (lane width, curvature, and vertical clearance) and allowable vehicle dimensions. For passenger vehicles operating on freeway roads, the result is a required lateral error bound of 0.57 m (0.20 m, 95%), a longitudinal bound of 1.40 m (0.48 m, 95%), a vertical bound of 1.30 m (0.43 m, 95%), and an attitude bound in each direction of 1.50 deg (0.51 deg, 95%). On local streets, the road geometry makes requirements more stringent where lateral and longitudinal error bounds of 0.29 m (0.10 m, 95%) are needed with an orientation requirement of 0.50 deg (0.17 deg, 95%).

Genetic interactions provide a powerful perspective into gene function, but our knowledge of the specific mechanisms that give rise to these interactions is still relatively limited. The availability of a global genetic interaction map in Saccharomyces cerevisiae, covering~30% of all possible double mutant combinations, provides an unprecedented opportunity for an unbiased assessment of the native structure within genetic interaction networks and how it relates to gene function and modular organization. Toward this end, we developed a data mining approach to exhaustively discover all block structures within this network, which allowed for its complete modular decomposition. The resulting modular structures revealed the importance of the context of individual genetic interactions in their interpretation and revealed distinct trends among genetic interaction hubs as well as insights into the evolution of duplicate genes. Block membership also revealed a surprising degree of multifunctionality across the yeast genome and enabled a novel association of VIP1 and IPK1 with DNA replication and repair, which is supported by experimental evidence. Our modular decomposition also provided a basis for testing the between-pathway model of negative genetic interactions and within-pathway model of positive genetic interactions. While we find that most modular structures involving negative genetic interactions fit the betweenpathway model, we found that current models for positive genetic interactions fail to explain 80% of the modular structures detected. We also find differences between the modular structures of essential and nonessential genes.

We propose an approach for external calibration of a 3D laser scanner with an omnidirectional camera system. The utility of an accurate calibration is that it allows for precise co-registration between the camera imagery and the 3D point cloud. This association can be used to enhance various state of the art algorithms in computer vision and robotics. The extrinsic calibration technique used here is similar to the calibration of a 2D laser range finder and a single camera as proposed by Zhang (2004), but has been extended to the case where we have a 3D laser scanner and an omnidirectional camera system. The procedure requires a planar checkerboard pattern to be observed simultaneously from the laser scanner and the camera system from a minimum of 3 views. The normal of the planar surface and 3D points lying on the surface constrain the relative position and orientation of the laser scanner and the omnidirectional camera system. These constraints can be used to form a non-linear optimization problem that is solved for the extrinsic calibration parameters and the covariance associated with the estimated parameters. Results are presented for a real world data set collected by a vehicle mounted with a 3D laser scanner and an omnidirectional camera system.

Genetic interactions occur when a combination of mutations results in a surprising phenotype. These interactions capture functional redundancy, and thus are important for predicting function, dissecting protein complexes into functional pathways, and exploring the mechanistic underpinnings of common human diseases. Synthetic sickness and lethality are the most studied types of genetic interactions in yeast. However, even in yeast, only a small proportion of gene pairs have been tested for genetic interactions due to the large number of possible combinations of gene pairs. To expand the set of known synthetic lethal (SL) interactions, we have devised an integrative, multi-network approach for predicting these interactions that significantly improves upon the existing approaches. First, we defined a large number of features for characterizing the relationships between pairs of genes from various data sources. In particular, these features are independent of the known SL interactions, in contrast to some previous approaches. Using these features, we developed a non-parametric multi-classifier system for predicting SL interactions that enabled the simultaneous use of multiple classification procedures. Several comprehensive experiments demonstrated that the SL-independent features in conjunction with the advanced classification scheme led to an improved performance when compared to the current state of the art method. Using this approach, we derived the first yeast transcription factor genetic interaction network, part of which was well supported by literature. We also used this approach to predict SL interactions between all non-essential gene pairs in yeast (http://sage.fhcrc.org/downloads/downloads/predicted_yeast_genetic_interactions.zip). This integrative approach is expected to be more effective and robust in uncovering new genetic interactions from the tens of millions of unknown gene pairs in yeast and from the hundreds of millions of gene pairs in higher organisms like mouse and human, in which very few genetic interactions have been identified to date.