Inferring Biologically Relevant Models: Nested Canalyzing Functions

Inferring dynamic biochemical networks is one of the main challenges in systems biology. Given experimental data, the objective is to identify the rules of interaction among the different entities of the network. However, the number of possible models fitting the available data is huge and identifying a biologically relevant model is of great interest. Nested canalyzing functions, where variables in a given order dominate the function, have recently been proposed as a framework for modeling gene regulatory networks. Previously we described this class of functions as an algebraic toric variety. In this paper, we present an algorithm that identifies all nested canalyzing models that fit the given data. We demonstrate our methods using a well-known Boolean model of the cell cycle in budding yeast

PinMe: Tracking a Smartphone User around the World

With the pervasive use of smartphones that sense, collect, and process valuable information about the environment, ensuring location privacy has become one of the most important concerns in the modern age. A few recent research studies discuss the feasibility of processing data gathered by a smartphone to locate the phone's owner, even when the user does not intend to share his location information, e.g., when the Global Positioning System (GPS) is off. Previous research efforts rely on at least one of the two following fundamental requirements, which significantly limit the ability of the adversary: (i) the attacker must accurately know either the user's initial location or the set of routes through which the user travels and/or (ii) the attacker must measure a set of features, e.g., the device's acceleration, for potential routes in advance and construct a training dataset. In this paper, we demonstrate that neither of the above-mentioned requirements is essential for compromising the user's location privacy. We describe PinMe, a novel user-location mechanism that exploits non-sensory/sensory data stored on the smartphone, e.g., the environment's air pressure, along with publicly-available auxiliary information, e.g., elevation maps, to estimate the user's location when all location services, e.g., GPS, are turned off.Comment: This is the preprint version: the paper has been published in IEEE Trans. Multi-Scale Computing Systems, DOI: 0.1109/TMSCS.2017.275146

Revealing Dynamic Mechanisms of Cell Fate Decisions From Single-Cell Transcriptomic Data.

Cell fate decisions play a pivotal role in development, but technologies for dissecting them are limited. We developed a multifunction new method, Topographer, to construct a "quantitative" Waddington's landscape of single-cell transcriptomic data. This method is able to identify complex cell-state transition trajectories and to estimate complex cell-type dynamics characterized by fate and transition probabilities. It also infers both marker gene networks and their dynamic changes as well as dynamic characteristics of transcriptional bursting along the cell-state transition trajectories. Applying this method to single-cell RNA-seq data on the differentiation of primary human myoblasts, we not only identified three known cell types, but also estimated both their fate probabilities and transition probabilities among them. We found that the percent of genes expressed in a bursty manner is significantly higher at (or near) the branch point (~97%) than before or after branch (below 80%), and that both gene-gene and cell-cell correlation degrees are apparently lower near the branch point than away from the branching. Topographer allows revealing of cell fate mechanisms in a coherent way at three scales: cell lineage (macroscopic), gene network (mesoscopic), and gene expression (microscopic)

The Effects of Population Size Histories on Estimates of Selection Coefficients from Time-Series Genetic Data.

Many approaches have been developed for inferring selection coefficients from time series data while accounting for genetic drift. These approaches have been motivated by the intuition that properly accounting for the population size history can significantly improve estimates of selective strengths. However, the improvement in inference accuracy that can be attained by modeling drift has not been characterized. Here, by comparing maximum likelihood estimates of selection coefficients that account for the true population size history with estimates that ignore drift by assuming allele frequencies evolve deterministically in a population of infinite size, we address the following questions: how much can modeling the population size history improve estimates of selection coefficients? How much can mis-inferred population sizes hurt inferences of selection coefficients? We conduct our analysis under the discrete Wright-Fisher model by deriving the exact probability of an allele frequency trajectory in a population of time-varying size and we replicate our results under the diffusion model. For both models, we find that ignoring drift leads to estimates of selection coefficients that are nearly as accurate as estimates that account for the true population history, even when population sizes are small and drift is high. This result is of interest because inference methods that ignore drift are widely used in evolutionary studies and can be many orders of magnitude faster than methods that account for population sizes