In supervised learning, we leverage a labeled dataset to design methods for function estimation. In many practical situations, we are able to obtain alternative feedback, possibly at a low cost. A broad goal is to understand the usefulness of, and to design algorithms to exploit, this alternative feedback. We focus on a semi-supervised setting where we obtain additional ordinal (or comparison) information for potentially unlabeled samples. We consider ordinal feedback of varying qualities where we have either a perfect ordering of the samples, a noisy ordering of the samples or noisy pairwise comparisons between the samples. We provide a precise quantification of the usefulness of these types of ordinal feedback in non-parametric regression, showing that in many cases it is possible to accurately estimate an underlying function with a very small labeled set, effectively escaping the curse of dimensionality. We develop an algorithm called Ranking-Regression (RR) and analyze its accuracy as a function of size of the labeled and unlabeled datasets and various noise parameters. We also present lower bounds, that establish fundamental limits for the task and show that RR is optimal in a variety of settings. Finally, we present experiments that show the efficacy of RR and investigate its robustness to various sources of noise and model-misspecification.

MOTIVATION: Cellular Electron CryoTomography (CECT) enables 3D visualization of cellular organization at near-native state and in sub-molecular resolution, making it a powerful tool for analyzing structures of macromolecular complexes and their spatial organizations inside single cells. However, high degree of structural complexity together with practical imaging limitations makes the systematic de novo discovery of structures within cells challenging. It would likely require averaging and classifying millions of subtomograms potentially containing hundreds of highly heterogeneous structural classes. Although it is no longer difficult to acquire CECT data containing such amount of subtomograms due to advances in data acquisition automation, existing computational approaches have very limited scalability or discrimination ability, making them incapable of processing such amount of data. RESULTS: To complement existing approaches, in this article we propose a new approach for subdividing subtomograms into smaller but relatively homogeneous subsets. The structures in these subsets can then be separately recovered using existing computation intensive methods. Our approach is based on supervised structural feature extraction using deep learning, in combination with unsupervised clustering and reference-free classification. Our experiments show that, compared with existing unsupervised rotation invariant feature and pose-normalization based approaches, our new approach achieves significant improvements in both discrimination ability and scalability. More importantly, our new approach is able to discover new structural classes and recover structures that do not exist in training data. AVAILABILITY AND IMPLEMENTATION: Source code freely available at http://www.cs.cmu.edu/∼mxu1/software . CONTACT: [email protected]. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.