Gradient matching methods for computational inference in mechanistic models for systems biology: a review and comparative analysis

Parameter inference in mathematical models of biological pathways, expressed as coupled ordinary differential equations (ODEs), is a challenging problem in contemporary systems biology. Conventional methods involve repeatedly solving the ODEs by numerical integration, which is computationally onerous and does not scale up to complex systems. Aimed at reducing the computational costs, new concepts based on gradient matching have recently been proposed in the computational statistics and machine learning literature. In a preliminary smoothing step, the time series data are interpolated; then, in a second step, the parameters of the ODEs are optimised so as to minimise some metric measuring the difference between the slopes of the tangents to the interpolants, and the time derivatives from the ODEs. In this way, the ODEs never have to be solved explicitly. This review provides a concise methodological overview of the current state-of-the-art methods for gradient matching in ODEs, followed by an empirical comparative evaluation based on a set of widely used and representative benchmark data

Kernel Belief Propagation

We propose a nonparametric generalization of belief propagation, Kernel Belief Propagation (KBP), for pairwise Markov random fields. Messages are represented as functions in a reproducing kernel Hilbert space (RKHS), and message updates are simple linear operations in the RKHS. KBP makes none of the assumptions commonly required in classical BP algorithms: the variables need not arise from a finite domain or a Gaussian distribution, nor must their relations take any particular parametric form. Rather, the relations between variables are represented implicitly, and are learned nonparametrically from training data. KBP has the advantage that it may be used on any domain where kernels are defined (Rd, strings, groups), even where explicit parametric models are not known, or closed form expressions for the BP updates do not exist. The computational cost of message updates in KBP is polynomial in the training data size. We also propose a constant time approximate message update procedure by representing messages using a small number of basis functions. In experiments, we apply KBP to image denoising, depth prediction from still images, and protein configuration prediction: KBP is faster than competing classical and nonparametric approaches (by orders of magnitude, in some cases), while providing significantly more accurate results

Hybrid approximate message passing

Gaussian and quadratic approximations of message passing algorithms on graphs have attracted considerable recent attention due to their computational simplicity, analytic tractability, and wide applicability in optimization and statistical inference problems. This paper presents a systematic framework for incorporating such approximate message passing (AMP) methods in general graphical models. The key concept is a partition of dependencies of a general graphical model into strong and weak edges, with the weak edges representing interactions through aggregates of small, linearizable couplings of variables. AMP approximations based on the Central Limit Theorem can be readily applied to aggregates of many weak edges and integrated with standard message passing updates on the strong edges. The resulting algorithm, which we call hybrid generalized approximate message passing (HyGAMP), can yield significantly simpler implementations of sum-product and max-sum loopy belief propagation. By varying the partition of strong and weak edges, a performance--complexity trade-off can be achieved. Group sparsity and multinomial logistic regression problems are studied as examples of the proposed methodology.The work of S. Rangan was supported in part by the National Science Foundation under Grants 1116589, 1302336, and 1547332, and in part by the industrial affiliates of NYU WIRELESS. The work of A. K. Fletcher was supported in part by the National Science Foundation under Grants 1254204 and 1738286 and in part by the Office of Naval Research under Grant N00014-15-1-2677. The work of V. K. Goyal was supported in part by the National Science Foundation under Grant 1422034. The work of E. Byrne and P. Schniter was supported in part by the National Science Foundation under Grant CCF-1527162. (1116589 - National Science Foundation; 1302336 - National Science Foundation; 1547332 - National Science Foundation; 1254204 - National Science Foundation; 1738286 - National Science Foundation; 1422034 - National Science Foundation; CCF-1527162 - National Science Foundation; NYU WIRELESS; N00014-15-1-2677 - Office of Naval Research