In computational histopathology algorithms now outperform humans on a range of tasks, but to date none are employed for automated diagnoses in the clinic. Before algorithms can be involved in such high-stakes decisions they need to "know when they don't know", i.e., they need to estimate their predictive uncertainty. This allows them to defer potentially erroneous predictions to a human pathologist, thus increasing their safety. Here, we evaluate the predictive performance and calibration of several uncertainty estimation methods on clinical histopathology data. We show that a distance-aware uncertainty estimation method outperforms commonly used approaches, such as Monte Carlo dropout and deep ensembles. However, we observe a drop in predictive performance and calibration on novel samples across all uncertainty estimation methods tested. We also investigate the use of uncertainty thresholding to reject out-of-distribution samples for selective prediction. We demonstrate the limitations of this approach and suggest areas for future research.

Startups often represent newly established business models associated with disruptive innovation and high scalability. They are commonly regarded as powerful engines for economic and social development. Meanwhile, startups are heavily constrained by many factors such as limited financial funding and human resources. Therefore the chance for a startup to eventually succeed is as rare as ``spotting a unicorn in the wild''. Venture Capital (VC) strives to identify and invest in unicorn startups during their early stages, hoping to gain a high return. To avoid entirely relying on human domain expertise and intuition, investors usually employ data-driven approaches to forecast the success probability of startups. Over the past two decades, the industry has gone through a paradigm shift moving from conventional statistical approaches towards becoming machine-learning (ML) based. Notably, the rapid growth of data volume and variety is quickly ushering in deep learning (DL), a subset of ML, as a potentially superior approach in terms capacity and expressivity. In this work, we carry out a literature review and synthesis on DL-based approaches, covering the entire DL life cycle. The objective is a) to obtain a thorough and in-depth understanding of the methodologies for startup evaluation using DL, and b) to distil valuable and actionable learning for practitioners. To the best of our knowledge, our work is the first of this kind.

We present consistent algorithms for multiclass learning with complex performance metrics and constraints, where the objective and constraints are defined by arbitrary functions of the confusion matrix. This setting includes many common performance metrics such as the multiclass G-mean and micro F1-measure, and constraints such as those on the classifier's precision and recall and more recent measures of fairness discrepancy. We give a general framework for designing consistent algorithms for such complex design goals by viewing the learning problem as an optimization problem over the set of feasible confusion matrices. We provide multiple instantiations of our framework under different assumptions on the performance metrics and constraints, and in each case show rates of convergence to the optimal (feasible) classifier (and thus asymptotic consistency). Experiments on a variety of multiclass classification tasks and fairness-constrained problems show that our algorithms compare favorably to the state-of-the-art baselines.

Graph anomaly detection in this paper aims to distinguish abnormal nodes that behave differently from the benign ones accounting for the majority of graph-structured instances. Receiving increasing attention from both academia and industry, yet existing research on this task still suffers from two critical issues when learning informative anomalous behavior from graph data. For one thing, anomalies are usually hard to capture because of their subtle abnormal behavior and the shortage of background knowledge about them, which causes severe anomalous sample scarcity. Meanwhile, the overwhelming majority of objects in real-world graphs are normal, bringing the class imbalance problem as well. To bridge the gaps, this paper devises a novel Data Augmentation-based Graph Anomaly Detection (DAGAD) framework for attributed graphs, equipped with three specially designed modules: 1) an information fusion module employing graph neural network encoders to learn representations, 2) a graph data augmentation module that fertilizes the training set with generated samples, and 3) an imbalance-tailored learning module to discriminate the distributions of the minority (anomalous) and majority (normal) classes. A series of experiments on three datasets prove that DAGAD outperforms ten state-of-the-art baseline detectors concerning various mostly-used metrics, together with an extensive ablation study validating the strength of our proposed modules.

Machine learning (ML) formalizes the problem of getting computers to learn from experience as optimization of performance according to some metric(s) on a set of data examples. This is in contrast to requiring behaviour specified in advance (e.g. by hard-coded rules). Formalization of this problem has enabled great progress in many applications with large real-world impact, including translation, speech recognition, self-driving cars, and drug discovery. But practical instantiations of this formalism make many assumptions - for example, that data are i.i.d.: independent and identically distributed - whose soundness is seldom investigated. And in making great progress in such a short time, the field has developed many norms and ad-hoc standards, focused on a relatively small range of problem settings. As applications of ML, particularly in artificial intelligence (AI) systems, become more pervasive in the real world, we need to critically examine these assumptions, norms, and problem settings, as well as the methods that have become de-facto standards. There is much we still do not understand about how and why deep networks trained with stochastic gradient descent are able to generalize as well as they do, why they fail when they do, and how they will perform on out-of-distribution data. In this thesis I cover some of my work towards better understanding deep net generalization, identify several ways assumptions and problem settings fail to generalize to the real world, and propose ways to address those failures in practice.

Existing vision-text contrastive learning like CLIP aims to match the paired image and caption embeddings while pushing others apart, which improves representation transferability and supports zero-shot prediction. However, medical image-text datasets are orders of magnitude below the general images and captions from the internet. Moreover, previous methods encounter many false negatives, i.e., images and reports from separate patients probably carry the same semantics but are wrongly treated as negatives. In this paper, we decouple images and texts for multimodal contrastive learning thus scaling the usable training data in a combinatorial magnitude with low cost. We also propose to replace the InfoNCE loss with semantic matching loss based on medical knowledge to eliminate false negatives in contrastive learning. We prove that MedCLIP is a simple yet effective framework: it outperforms state-of-the-art methods on zero-shot prediction, supervised classification, and image-text retrieval. Surprisingly, we observe that with only 20K pre-training data, MedCLIP wins over the state-of-the-art method (using around 200K data). Our code is available at https://github.com/RyanWangZf/MedCLIP.

Out-of-distribution (OOD) detection, i.e., finding test samples derived from a different distribution than the training set, as well as reasoning about such samples (OOD reasoning), are necessary to ensure the safety of results generated by machine learning models. Recently there have been promising results for OOD detection in the latent space of variational autoencoders (VAEs). However, without disentanglement, VAEs cannot perform OOD reasoning. Disentanglement ensures a one- to-many mapping between generative factors of OOD (e.g., rain in image data) and the latent variables to which they are encoded. Although previous literature has focused on weakly-supervised disentanglement on simple datasets with known and independent generative factors. In practice, achieving full disentanglement through weak supervision is impossible for complex datasets, such as Carla, with unknown and abstract generative factors. As a result, we propose an OOD reasoning framework that learns a partially disentangled VAE to reason about complex datasets. Our framework consists of three steps: partitioning data based on observed generative factors, training a VAE as a logic tensor network that satisfies disentanglement rules, and run-time OOD reasoning. We evaluate our approach on the Carla dataset and compare the results against three state-of-the-art methods. We found that our framework outperformed these methods in terms of disentanglement and end-to-end OOD reasoning.

Open-Set Classification (OSC) intends to adapt closed-set classification models to real-world scenarios, where the classifier must correctly label samples of known classes while rejecting previously unseen unknown samples. Only recently, research started to investigate on algorithms that are able to handle these unknown samples correctly. Some of these approaches address OSC by including into the training set negative samples that a classifier learns to reject, expecting that these data increase the robustness of the classifier on unknown classes. Most of these approaches are evaluated on small-scale and low-resolution image datasets like MNIST, SVHN or CIFAR, which makes it difficult to assess their applicability to the real world, and to compare them among each other. We propose three open-set protocols that provide rich datasets of natural images with different levels of similarity between known and unknown classes. The protocols consist of subsets of ImageNet classes selected to provide training and testing data closer to real-world scenarios. Additionally, we propose a new validation metric that can be employed to assess whether the training of deep learning models addresses both the classification of known samples and the rejection of unknown samples. We use the protocols to compare the performance of two baseline open-set algorithms to the standard SoftMax baseline and find that the algorithms work well on negative samples that have been seen during training, and partially on out-of-distribution detection tasks, but drop performance in the presence of samples from previously unseen unknown classes.

When a dynamical system can be modeled as a sequence of observations, Granger causality is a powerful approach for detecting predictive interactions between its variables. However, traditional Granger causal inference has limited utility in domains where the dynamics need to be represented as directed acyclic graphs (DAGs) rather than as a linear sequence, such as with cell differentiation trajectories. Here, we present GrID-Net, a framework based on graph neural networks with lagged message passing for Granger causal inference on DAG-structured systems. Our motivating application is the analysis of single-cell multimodal data to identify genomic loci that mediate the regulation of specific genes. To our knowledge, GrID-Net is the first single-cell analysis tool that accounts for the temporal lag between a genomic locus becoming accessible and its downstream effect on a target gene's expression. We applied GrID-Net on multimodal single-cell assays that profile chromatin accessibility (ATAC-seq) and gene expression (RNA-seq) in the same cell and show that it dramatically outperforms existing methods for inferring regulatory locus-gene links, achieving up to 71% greater agreement with independent population genetics-based estimates. By extending Granger causality to DAG-structured dynamical systems, our work unlocks new domains for causal analyses and, more specifically, opens a path towards elucidating gene regulatory interactions relevant to cellular differentiation and complex human diseases at unprecedented scale and resolution.

Industrial defect detection is commonly addressed with anomaly detection (AD) methods where no or only incomplete data of potentially occurring defects is available. This work discovers previously unknown problems of student-teacher approaches for AD and proposes a solution, where two neural networks are trained to produce the same output for the defect-free training examples. The core assumption of student-teacher networks is that the distance between the outputs of both networks is larger for anomalies since they are absent in training. However, previous methods suffer from the similarity of student and teacher architecture, such that the distance is undesirably small for anomalies. For this reason, we propose asymmetric student-teacher networks (AST). We train a normalizing flow for density estimation as a teacher and a conventional feed-forward network as a student to trigger large distances for anomalies: The bijectivity of the normalizing flow enforces a divergence of teacher outputs for anomalies compared to normal data. Outside the training distribution the student cannot imitate this divergence due to its fundamentally different architecture. Our AST network compensates for wrongly estimated likelihoods by a normalizing flow, which was alternatively used for anomaly detection in previous work. We show that our method produces state-of-the-art results on the two currently most relevant defect detection datasets MVTec AD and MVTec 3D-AD regarding image-level anomaly detection on RGB and 3D data.