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Joshua T. Vogelstein

Publications and source records attributed to Joshua T. Vogelstein.

At least 37 records · Page 2Linked to original sources

Independence Testing for Temporal Data

Temporal data are increasingly prevalent in modern data science. A fundamental question is whether two time series are related or not. Existing approaches often have limitations, such as relying on parametric assumptions, detecting only linear associations, and requiring multiple tests and corrections. While many non-parametric and universally consistent dependence measures have recently been proposed, directly applying them to temporal data can inflate the p-value and result in an invalid test. To address these challenges, this paper introduces the temporal dependence statistic with block permutation to test independence between temporal data. Under proper assumptions, the proposed procedure is asymptotically valid and universally consistent for testing independence between stationary time series, and capable of estimating the optimal dependence lag that maximizes the dependence. Moreover, it is compatible with a rich family of distance and kernel based dependence measures, eliminates the need for multiple testing, and exhibits excellent testing power in various simulation settings.

stat.ML↗

Approximately optimal domain adaptation with Fisher's Linear Discriminant

We propose a class of models based on Fisher's Linear Discriminant (FLD) in the context of domain adaptation. The class is the convex combination of two hypotheses: i) an average hypothesis representing previously seen source tasks and ii) a hypothesis trained on a new target task. For a particular generative setting we derive the optimal convex combination of the two models under 0-1 loss, propose a computable approximation, and study the effect of various parameter settings on the relative risks between the optimal hypothesis, hypothesis i), and hypothesis ii). We demonstrate the effectiveness of the proposed optimal classifier in the context of EEG- and ECG-based classification settings and argue that the optimal classifier can be computed without access to direct information from any of the individual source tasks. We conclude by discussing further applications, limitations, and possible future directions.

eess.SP↗

Learning sources of variability from high-dimensional observational studies

Causal inference studies whether the presence of a variable influences an observed outcome. As measured by quantities such as the "average treatment effect," this paradigm is employed across numerous biological fields, from vaccine and drug development to policy interventions. Unfortunately, the majority of these methods are often limited to univariate outcomes. Our work generalizes causal estimands to outcomes with any number of dimensions or any measurable space, and formulates traditional causal estimands for nominal variables as causal discrepancy tests. We propose a simple technique for adjusting universally consistent conditional independence tests and prove that these tests are universally consistent causal discrepancy tests. Numerical experiments illustrate that our method, Causal CDcorr, leads to improvements in both finite sample validity and power when compared to existing strategies. Our methods are all open source and available at github.com/ebridge2/cdcorr.

stat.ME↗

Why do networks have inhibitory/negative connections?

Why do brains have inhibitory connections? Why do deep networks have negative weights? We propose an answer from the perspective of representation capacity. We believe representing functions is the primary role of both (i) the brain in natural intelligence, and (ii) deep networks in artificial intelligence. Our answer to why there are inhibitory/negative weights is: to learn more functions. We prove that, in the absence of negative weights, neural networks with non-decreasing activation functions are not universal approximators. While this may be an intuitive result to some, to the best of our knowledge, there is no formal theory, in either machine learning or neuroscience, that demonstrates why negative weights are crucial in the context of representation capacity. Further, we provide insights on the geometric properties of the representation space that non-negative deep networks cannot represent. We expect these insights will yield a deeper understanding of more sophisticated inductive priors imposed on the distribution of weights that lead to more efficient biological and machine learning.

cs.LG↗

Preserving Derivative Information while Transforming Neuronal Curves

The international neuroscience community is building the first comprehensive atlases of brain cell types to understand how the brain functions from a higher resolution, and more integrated perspective than ever before. In order to build these atlases, subsets of neurons (e.g. serotonergic neurons, prefrontal cortical neurons etc.) are traced in individual brain samples by placing points along dendrites and axons. Then, the traces are mapped to common coordinate systems by transforming the positions of their points, which neglects how the transformation bends the line segments in between. In this work, we apply the theory of jets to describe how to preserve derivatives of neuron traces up to any order. We provide a framework to compute possible error introduced by standard mapping methods, which involves the Jacobian of the mapping transformation. We show how our first order method improves mapping accuracy in both simulated and real neuron traces under random diffeomorphisms. Our method is freely available in our open-source Python package brainlit.

q-bio.NC↗

Prospective Learning: Principled Extrapolation to the Future

Learning is a process which can update decision rules, based on past experience, such that future performance improves. Traditionally, machine learning is often evaluated under the assumption that the future will be identical to the past in distribution or change adversarially. But these assumptions can be either too optimistic or pessimistic for many problems in the real world. Real world scenarios evolve over multiple spatiotemporal scales with partially predictable dynamics. Here we reformulate the learning problem to one that centers around this idea of dynamic futures that are partially learnable. We conjecture that certain sequences of tasks are not retrospectively learnable (in which the data distribution is fixed), but are prospectively learnable (in which distributions may be dynamic), suggesting that prospective learning is more difficult in kind than retrospective learning. We argue that prospective learning more accurately characterizes many real world problems that (1) currently stymie existing artificial intelligence solutions and/or (2) lack adequate explanations for how natural intelligences solve them. Thus, studying prospective learning will lead to deeper insights and solutions to currently vexing challenges in both natural and artificial intelligences.

cs.LG↗

The Value of Out-of-Distribution Data

We expect the generalization error to improve with more samples from a similar task, and to deteriorate with more samples from an out-of-distribution (OOD) task. In this work, we show a counter-intuitive phenomenon: the generalization error of a task can be a non-monotonic function of the number of OOD samples. As the number of OOD samples increases, the generalization error on the target task improves before deteriorating beyond a threshold. In other words, there is value in training on small amounts of OOD data. We use Fisher's Linear Discriminant on synthetic datasets and deep networks on computer vision benchmarks such as MNIST, CIFAR-10, CINIC-10, PACS and DomainNet to demonstrate and analyze this phenomenon. In the idealistic setting where we know which samples are OOD, we show that these non-monotonic trends can be exploited using an appropriately weighted objective of the target and OOD empirical risk. While its practical utility is limited, this does suggest that if we can detect OOD samples, then there may be ways to benefit from them. When we do not know which samples are OOD, we show how a number of go-to strategies such as data-augmentation, hyper-parameter optimization, and pre-training are not enough to ensure that the target generalization error does not deteriorate with the number of OOD samples in the dataset.

cs.LG↗

Polarity is all you need to learn and transfer faster

Natural intelligences (NIs) thrive in a dynamic world - they learn quickly, sometimes with only a few samples. In contrast, artificial intelligences (AIs) typically learn with a prohibitive number of training samples and computational power. What design principle difference between NI and AI could contribute to such a discrepancy? Here, we investigate the role of weight polarity: development processes initialize NIs with advantageous polarity configurations; as NIs grow and learn, synapse magnitudes update, yet polarities are largely kept unchanged. We demonstrate with simulation and image classification tasks that if weight polarities are adequately set a priori, then networks learn with less time and data. We also explicitly illustrate situations in which a priori setting the weight polarities is disadvantageous for networks. Our work illustrates the value of weight polarities from the perspective of statistical and computational efficiency during learning.

cs.LG↗

Discovering a change point and piecewise linear structure in a time series of organoid networks via the iso-mirror

Recent advancements have been made in the development of cell-based in-vitro neuronal networks, or organoids. In order to better understand the network structure of these organoids, a super-selective algorithm has been proposed for inferring the effective connectivity networks from multi-electrode array data. In this paper, we apply a novel statistical method called spectral mirror estimation to the time series of inferred effective connectivity organoid networks. This method produces a one-dimensional iso-mirror representation of the dynamics of the time series of the networks which exhibits a piecewise linear structure. A classical change point algorithm is then applied to this representation, which successfully detects a change point coinciding with the neuroscientifically significant time inhibitory neurons start appearing and the percentage of astrocytes increases dramatically. This finding demonstrates the potential utility of applying the iso-mirror dynamic structure discovery method to inferred effective connectivity time series of organoid networks.

stat.AP↗

Federated Causal Inference in Heterogeneous Observational Data

We are interested in estimating the effect of a treatment applied to individuals at multiple sites, where data is stored locally for each site. Due to privacy constraints, individual-level data cannot be shared across sites; the sites may also have heterogeneous populations and treatment assignment mechanisms. Motivated by these considerations, we develop federated methods to draw inference on the average treatment effects of combined data across sites. Our methods first compute summary statistics locally using propensity scores and then aggregate these statistics across sites to obtain point and variance estimators of average treatment effects. We show that these estimators are consistent and asymptotically normal. To achieve these asymptotic properties, we find that the aggregation schemes need to account for the heterogeneity in treatment assignments and in outcomes across sites. We demonstrate the validity of our federated methods through a comparative study of two large medical claims databases.

cs.LG↗

Distance-based Positive and Unlabeled Learning for Ranking

Learning to rank -- producing a ranked list of items specific to a query and with respect to a set of supervisory items -- is a problem of general interest. The setting we consider is one in which no analytic description of what constitutes a good ranking is available. Instead, we have a collection of representations and supervisory information consisting of a (target item, interesting items set) pair. We demonstrate analytically, in simulation, and in real data examples that learning to rank via combining representations using an integer linear program is effective when the supervision is as light as "these few items are similar to your item of interest." While this nomination task is quite general, for specificity we present our methodology from the perspective of vertex nomination in graphs. The methodology described herein is model agnostic.

cs.LG↗

Manifold Oblique Random Forests: Towards Closing the Gap on Convolutional Deep Networks

Decision forests (Forests), in particular random forests and gradient boosting trees, have demonstrated state-of-the-art accuracy compared to other methods in many supervised learning scenarios. In particular, Forests dominate other methods in tabular data, that is, when the feature space is unstructured, so that the signal is invariant to a permutation of the feature indices. However, in structured data lying on a manifold (such as images, text, and speech) deep networks (Networks), specifically convolutional deep networks (ConvNets), tend to outperform Forests. We conjecture that at least part of the reason for this is that the input to Networks is not simply the feature magnitudes, but also their indices. In contrast, naive Forest implementations fail to explicitly consider feature indices. A recently proposed Forest approach demonstrates that Forests, for each node, implicitly sample a random matrix from some specific distribution. These Forests, like some classes of Networks, learn by partitioning the feature space into convex polytopes corresponding to linear functions. We build on that approach and show that one can choose distributions in a manifold-aware fashion to incorporate feature locality. We demonstrate the empirical performance on data whose features live on three different manifolds: a torus, images, and time-series. Moreover, we demonstrate its strength in multivariate simulated settings and also show superiority in predicting surgical outcome in epilepsy patients and predicting movement direction from raw stereotactic EEG data from non-motor brain regions. In all simulations and real data, Manifold Oblique Random Forest (MORF) algorithm outperforms approaches that ignore feature space structure and challenges the performance of ConvNets. Moreover, MORF runs fast and maintains interpretability and theoretical justification.

cs.LG↗

Hidden Markov Modeling for Maximum Likelihood Neuron Reconstruction

Recent advances in brain clearing and imaging have made it possible to image entire mammalian brains at sub-micron resolution. These images offer the potential to assemble brain-wide atlases of neuron morphology, but manual neuron reconstruction remains a bottleneck. Several automatic reconstruction algorithms exist, but most focus on single neuron images. In this paper, we present a probabilistic reconstruction method, ViterBrain, which combines a hidden Markov state process that encodes neuron geometry with a random field appearance model of neuron fluorescence. Our method utilizes dynamic programming to compute the global maximizers of what we call the "most probable" neuron path. Our most probable estimation method models the task of reconstructing neuronal processes in the presence of other neurons, and thus is applicable in images with several neurons. Our method operates on image segmentations in order to leverage cutting edge computer vision technology. We applied our algorithm to imperfect image segmentations where false negatives severed neuronal processes, and showed that it can follow axons in the presence of noise or nearby neurons. Additionally, it creates a framework where users can intervene to, for example, fit start and endpoints. The code used in this work is available in our open-source Python package brainlit.

cs.CV↗

Graph Matching via Optimal Transport

The graph matching problem seeks to find an alignment between the nodes of two graphs that minimizes the number of adjacency disagreements. Solving the graph matching is increasingly important due to it's applications in operations research, computer vision, neuroscience, and more. However, current state-of-the-art algorithms are inefficient in matching very large graphs, though they produce good accuracy. The main computational bottleneck of these algorithms is the linear assignment problem, which must be solved at each iteration. In this paper, we leverage the recent advances in the field of optimal transport to replace the accepted use of linear assignment algorithms. We present GOAT, a modification to the state-of-the-art graph matching approximation algorithm "FAQ" (Vogelstein, 2015), replacing its linear sum assignment step with the "Lightspeed Optimal Transport" method of Cuturi (2013). The modification provides improvements to both speed and empirical matching accuracy. The effectiveness of the approach is demonstrated in matching graphs in simulated and real data examples.

stat.ML↗

When are Deep Networks really better than Decision Forests at small sample sizes, and how?

Deep networks and decision forests (such as random forests and gradient boosted trees) are the leading machine learning methods for structured and tabular data, respectively. Many papers have empirically compared large numbers of classifiers on one or two different domains (e.g., on 100 different tabular data settings). However, a careful conceptual and empirical comparison of these two strategies using the most contemporary best practices has yet to be performed. Conceptually, we illustrate that both can be profitably viewed as "partition and vote" schemes. Specifically, the representation space that they both learn is a partitioning of feature space into a union of convex polytopes. For inference, each decides on the basis of votes from the activated nodes. This formulation allows for a unified basic understanding of the relationship between these methods. Empirically, we compare these two strategies on hundreds of tabular data settings, as well as several vision and auditory settings. Our focus is on datasets with at most 10,000 samples, which represent a large fraction of scientific and biomedical datasets. In general, we found forests to excel at tabular and structured data (vision and audition) with small sample sizes, whereas deep nets performed better on structured data with larger sample sizes. This suggests that further gains in both scenarios may be realized via further combining aspects of forests and networks. We will continue revising this technical report in the coming months with updated results.

cs.LG↗

Random Forests for Adaptive Nearest Neighbor Estimation of Information-Theoretic Quantities

Information-theoretic quantities, such as conditional entropy and mutual information, are critical data summaries for quantifying uncertainty. Current widely used approaches for computing such quantities rely on nearest neighbor methods and exhibit both strong performance and theoretical guarantees in certain simple scenarios. However, existing approaches fail in high-dimensional settings and when different features are measured on different scales.We propose decision forest-based adaptive nearest neighbor estimators and show that they are able to effectively estimate posterior probabilities, conditional entropies, and mutual information even in the aforementioned settings.We provide an extensive study of efficacy for classification and posterior probability estimation, and prove certain forest-based approaches to be consistent estimators of the true posteriors and derived information-theoretic quantities under certain assumptions. In a real-world connectome application, we quantify the uncertainty about neuron type given various cellular features in the Drosophila larva mushroom body, a key challenge for modern neuroscience.

cs.LG↗

Valid Two-Sample Graph Testing via Optimal Transport Procrustes and Multiscale Graph Correlation with Applications in Connectomics

Testing whether two graphs come from the same distribution is of interest in many real world scenarios, including brain network analysis. Under the random dot product graph model, the nonparametric hypothesis testing frame-work consists of embedding the graphs using the adjacency spectral embedding (ASE), followed by aligning the embeddings using the median flip heuristic, and finally applying the nonparametric maximum mean discrepancy(MMD) test to obtain a p-value. Using synthetic data generated from Drosophila brain networks, we show that the median flip heuristic results in an invalid test, and demonstrate that optimal transport Procrustes (OTP) for alignment resolves the invalidity. We further demonstrate that substituting the MMD test with multiscale graph correlation(MGC) test leads to a more powerful test both in synthetic and in simulated data. Lastly, we apply this powerful test to the right and left hemispheres of the larval Drosophila mushroom body brain networks, and conclude that there is not sufficient evidence to reject the null hypothesis that the two hemispheres are equally distributed.

stat.ME↗

Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection

In severe viral pneumonia, including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by hyperinflammation, which can lead to acute respiratory distress syndrome, multi-organ failure, and death. We previously demonstrated that alpha-1 adrenergic receptor ($α_1$-AR) antagonists can prevent hyperinflammation and death in mice. Here, we conducted retrospective analyses in two cohorts of patients with acute respiratory distress (ARD, n=18,547) and three cohorts with pneumonia (n=400,907). Federated across two ARD cohorts, we find that patients exposed to $α_1$-AR antagonists, as compared to unexposed patients, had a 34% relative risk reduction for mechanical ventilation and death (OR=0.70, p=0.021). We replicated these methods on three pneumonia cohorts, all with similar effects on both outcomes. All results were robust to sensitivity analyses. These results highlight the urgent need for prospective trials testing whether prophylactic use of $α_1$-AR antagonists ameliorates lower respiratory tract infection-associated hyperinflammation and death, as observed in COVID-19.

q-bio.TO↗