Kernel-based Inference of Functions over Graphs

The study of networks has witnessed an explosive growth over the past decades with several ground-breaking methods introduced. A particularly interesting -- and prevalent in several fields of study -- problem is that of inferring a function defined over the nodes of a network. This work presents a versatile kernel-based framework for tackling this inference problem that naturally subsumes and generalizes the reconstruction approaches put forth recently by the signal processing on graphs community. Both the static and the dynamic settings are considered along with effective modeling approaches for addressing real-world problems. The herein analytical discussion is complemented by a set of numerical examples, which showcase the effectiveness of the presented techniques, as well as their merits related to state-of-the-art methods.Comment: To be published as a chapter in `Adaptive Learning Methods for Nonlinear System Modeling', Elsevier Publishing, Eds. D. Comminiello and J.C. Principe (2018). This chapter surveys recent work on kernel-based inference of functions over graphs including arXiv:1612.03615 and arXiv:1605.07174 and arXiv:1711.0930

Elements and evolutionary determinants of genomic divergence between paired primary and metastatic tumors.

Can metastatic-primary (M-P) genomic divergence measured from next generation sequencing reveal the natural history of metastatic dissemination? This remains an open question of utmost importance in facilitating a deeper understanding of metastatic progression, and thereby, improving its prevention. Here, we utilize mathematical and computational modeling to tackle this question as well as to provide a framework that illuminates the fundamental elements and evolutionary determinants of M-P divergence. Our framework facilitates the integration of sequencing detectability of somatic variants, and hence, paves the way towards bridging the measurable between-tumor heterogeneity with analytical modeling and interpretability. We show that the number of somatic variants of the metastatic seeding cell that are experimentally undetectable in the primary tumor, can be characterized as the path of the phylogenetic tree from the last appearing variant of the seeding cell back to the most recent detectable variant. We find that the expected length of this path is principally determined by the decay in detectability of the variants along the seeding cell's lineage; and thus, exhibits a significant dependence on the underlying tumor growth dynamics. A striking implication of this fact, is that dissemination from an advanced detectable subclone of the primary tumor can lead to an abrupt drop in the expected measurable M-P divergence, thereby breaking the previously assumed monotonic relation between seeding time and M-P divergence. This is emphatically verified by our single cell-based spatial tumor growth simulation, where we find that M-P divergence exhibits a non-monotonic relationship with seeding time when the primary tumor grows under branched and linear evolution. On the other hand, a monotonic relationship holds when we condition on the dynamics of progressive diversification, or by restricting the seeding cells to always originate from undetectable subclones. Our results highlight the fact that a precise understanding of tumor growth dynamics is the sine qua non for exploiting M-P divergence to reconstruct the chronology of metastatic dissemination. The quantitative models presented here enable further careful evaluation of M-P divergence in association with crucial evolutionary and sequencing parameters

Hybrid ADMM: a unifying and fast approach to decentralized optimization

Abstract The present work introduces the hybrid consensus alternating direction method of multipliers (H-CADMM), a novel framework for optimization over networks which unifies existing distributed optimization approaches, including the centralized and the decentralized consensus ADMM. H-CADMM provides a flexible tool that leverages the underlying graph topology in order to achieve a desirable sweet spot between node-to-node communication overhead and rate of convergence—thereby alleviating known limitations of both C-CADMM and D-CADMM. A rigorous analysis of the novel method establishes linear convergence rate and also guides the choice of parameters to optimize this rate. The novel hybrid update rules of H-CADMM lend themselves to “in-network acceleration” that is shown to effect considerable—and essentially “free-of-charge”—performance boost over the fully decentralized ADMM. Comprehensive numerical tests validate the analysis and showcase the potential of the method in tackling efficiently, widely useful learning tasks