A Bayesian approach for inferring neuronal connectivity from calcium fluorescent imaging data

Deducing the structure of neural circuits is one of the central problems of modern neuroscience. Recently-introduced calcium fluorescent imaging methods permit experimentalists to observe network activity in large populations of neurons, but these techniques provide only indirect observations of neural spike trains, with limited time resolution and signal quality. In this work we present a Bayesian approach for inferring neural circuitry given this type of imaging data. We model the network activity in terms of a collection of coupled hidden Markov chains, with each chain corresponding to a single neuron in the network and the coupling between the chains reflecting the network's connectivity matrix. We derive a Monte Carlo Expectation--Maximization algorithm for fitting the model parameters; to obtain the sufficient statistics in a computationally-efficient manner, we introduce a specialized blockwise-Gibbs algorithm for sampling from the joint activity of all observed neurons given the observed fluorescence data. We perform large-scale simulations of randomly connected neuronal networks with biophysically realistic parameters and find that the proposed methods can accurately infer the connectivity in these networks given reasonable experimental and computational constraints. In addition, the estimation accuracy may be improved significantly by incorporating prior knowledge about the sparseness of connectivity in the network, via standard L$_1$ penalization methods.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS303 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Covariate-assisted spectral clustering

Biological and social systems consist of myriad interacting units. The interactions can be represented in the form of a graph or network. Measurements of these graphs can reveal the underlying structure of these interactions, which provides insight into the systems that generated the graphs. Moreover, in applications such as connectomics, social networks, and genomics, graph data are accompanied by contextualizing measures on each node. We utilize these node covariates to help uncover latent communities in a graph, using a modification of spectral clustering. Statistical guarantees are provided under a joint mixture model that we call the node-contextualized stochastic blockmodel, including a bound on the mis-clustering rate. The bound is used to derive conditions for achieving perfect clustering. For most simulated cases, covariate-assisted spectral clustering yields results superior to regularized spectral clustering without node covariates and to an adaptation of canonical correlation analysis. We apply our clustering method to large brain graphs derived from diffusion MRI data, using the node locations or neurological region membership as covariates. In both cases, covariate-assisted spectral clustering yields clusters that are easier to interpret neurologically.Comment: 28 pages, 4 figures, includes substantial changes to theoretical result

Nonparametric Bayes Modeling of Populations of Networks

Replicated network data are increasingly available in many research fields. In connectomic applications, inter-connections among brain regions are collected for each patient under study, motivating statistical models which can flexibly characterize the probabilistic generative mechanism underlying these network-valued data. Available models for a single network are not designed specifically for inference on the entire probability mass function of a network-valued random variable and therefore lack flexibility in characterizing the distribution of relevant topological structures. We propose a flexible Bayesian nonparametric approach for modeling the population distribution of network-valued data. The joint distribution of the edges is defined via a mixture model which reduces dimensionality and efficiently incorporates network information within each mixture component by leveraging latent space representations. The formulation leads to an efficient Gibbs sampler and provides simple and coherent strategies for inference and goodness-of-fit assessments. We provide theoretical results on the flexibility of our model and illustrate improved performance --- compared to state-of-the-art models --- in simulations and application to human brain networks

The Exact Equivalence of Distance and Kernel Methods for Hypothesis Testing

Distance-based tests, also called "energy statistics", are leading methods for two-sample and independence tests from the statistics community. Kernel-based tests, developed from "kernel mean embeddings", are leading methods for two-sample and independence tests from the machine learning community. A fixed-point transformation was previously proposed to connect the distance methods and kernel methods for the population statistics. In this paper, we propose a new bijective transformation between metrics and kernels. It simplifies the fixed-point transformation, inherits similar theoretical properties, allows distance methods to be exactly the same as kernel methods for sample statistics and p-value, and better preserves the data structure upon transformation. Our results further advance the understanding in distance and kernel-based tests, streamline the code base for implementing these tests, and enable a rich literature of distance-based and kernel-based methodologies to directly communicate with each other.Comment: 24 pages main + 7 pages appendix, 3 figure