Sample-efficient identification of high-dimensional antibiotic synergy with a normalized diagonal sampling design.

Antibiotic resistance is an important public health problem. One potential solution is the development of synergistic antibiotic combinations, in which the combination is more effective than the component drugs. However, experimental progress in this direction is severely limited by the number of samples required to exhaustively test for synergy, which grows exponentially with the number of drugs combined. We introduce a new metric for antibiotic synergy, motivated by the popular Fractional Inhibitory Concentration Index and the Highest Single Agent model. We also propose a new experimental design that samples along all appropriately normalized diagonals in concentration space, and prove that this design identifies all synergies among a set of drugs while only sampling a small fraction of the possible combinations. We applied our method to screen two- through eight-way combinations of eight antibiotics at 10 concentrations each, which requires sampling only 2,560 unique combinations of antibiotic concentrations.

The Extreme Value Machine.

It is often desirable to be able to recognize when inputs to a recognition function learned in a supervised manner correspond to classes unseen at training time. With this ability, new class labels could be assigned to these inputs by a human operator, allowing them to be incorporated into the recognition function-ideally under an efficient incremental update mechanism. While good algorithms that assume inputs from a fixed set of classes exist, e.g. , artificial neural networks and kernel machines, it is not immediately obvious how to extend them to perform incremental learning in the presence of unknown query classes. Existing algorithms take little to no distributional information into account when learning recognition functions and lack a strong theoretical foundation. We address this gap by formulating a novel, theoretically sound classifier-the Extreme Value Machine (EVM). The EVM has a well-grounded interpretation derived from statistical Extreme Value Theory (EVT), and is the first classifier to be able to perform nonlinear kernel-free variable bandwidth incremental learning. Compared to other classifiers in the same deep network derived feature space, the EVM is accurate and efficient on an established benchmark partition of the ImageNet dataset.

Probability Models for Open Set Recognition.

Real-world tasks in computer vision often touch upon open set recognition: multi-class recognition with incomplete knowledge of the world and many unknown inputs. Recent work on this problem has proposed a model incorporating an open space risk term to account for the space beyond the reasonable support of known classes. This paper extends the general idea of open space risk limiting classification to accommodate non-linear classifiers in a multiclass setting. We introduce a new open set recognition model called compact abating probability (CAP), where the probability of class membership decreases in value (abates) as points move from known data toward open space. We show that CAP models improve open set recognition for multiple algorithms. Leveraging the CAP formulation, we go on to describe the novel Weibull-calibrated SVM (W-SVM) algorithm, which combines the useful properties of statistical extreme value theory for score calibration with one-class and binary support vector machines. Our experiments show that the W-SVM is significantly better for open set object detection and OCR problems when compared to the state-of-the-art for the same tasks.