Data Assimilation for Sign-indefinite Priors: A generalization of Sinkhorn's algorithm

The purpose of this work is to develop a framework to calibrate signed datasets so as to be consistent with specified marginals by suitably extending the Schr\"odinger-Fortet-Sinkhorn paradigm. Specifically, we seek to revise sign-indefinite multi-dimensional arrays in a way that the updated values agree with specified marginals. Our approach follows the rationale in Schr\"odinger's problem, aimed at updating a "prior" probability measure to agree with marginal distributions. The celebrated Sinkhorn's algorithm (established earlier by R.\ Fortet) that solves Schr\"odinger's problem found early applications in calibrating contingency tables in statistics and, more recently, multi-marginal problems in machine learning and optimal transport. Herein, we postulate a sign-indefinite prior in the form of a multi-dimensional array, and propose an optimization problem to suitably update this prior to ensure consistency with given marginals. The resulting algorithm generalizes the Sinkhorn algorithm in that it amounts to iterative scaling of the entries of the array along different coordinate directions. The scaling is multiplicative but also, in contrast to Sinkhorn, inverse-multiplicative depending on the sign of the entries. Our algorithm reduces to the classical Sinkhorn algorithm when the entries of the prior are positive.

Negative probabilities in Gene Regulatory Networks

We introduce a natural framework to identify sign-indefinite co-expressions between genes based on the known expressions and given the sign of their respective correlations. Specifically, given information concerning the affinity among genes (i.e., connectivity in the gene regulatory network) and knowledge whether they promote/inhibit co-expression of the respective protein production, we seek rates that may explain the observed stationary distributions at the level of proteins. We propose to encapsulate their ``promotion vs.\ inhibition'' functionality in a sign-indefinite probability transition matrix--a matrix whose row-sums equal to one, but is otherwise sign indefinite. The purpose of constructing such a representation for the interaction network with sign-indefinite contributions in protein regulation, is to quantify the structure and significance of various links, and to explain how these may affect the geometry of the network, highlighting the significance of the regulatory functions of certain genes. We cast the problem of finding the interaction (sign-indefinite) transition matrix as a solution to a convex optimization problem from which all the relevant geometric properties may be easily derived.