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Natural odors typically consist of many molecules at different concentrations. It is unclear how the numerous odorant molecules and their possible mixtures are discriminated by relatively few olfactory receptors. Using an…
This thesis is designed to be a self-contained exposition of the neurobiological and mathematical aspects of sensory perception, memory, and learning with a bias towards olfaction. The final chapters introduce a new approach to modeling…
The study of gene regulation and expression is often discussed in quantitative terms. In particular, the expression of genes is regularly characterized with respect to how much, how fast, when and where. Whether discussing the level of gene…
We introduce a novel method to screen the promoters of a set of genes with shared biological function, against a precompiled library of motifs, and find those motifs which are statistically over-represented in the gene set. The gene sets…
Modeling the preferences of agents over a set of alternatives is a principal concern in many areas. The dominant approach has been to find a single reward/utility function with the property that alternatives yielding higher rewards are…
In the simplest view of transcriptional regulation, the expression of a gene is turned on or off by changes in the concentration of a transcription factor (TF). We use recent data on noise levels in gene expression to show that it should be…
Much of the genome is expressed in the vertebrate brain, with individual genes exhibiting different spatially-varying patterns of expression. These variations are not independent, with pairs of genes exhibiting complex patterns of…
Many DNA sequence variants influence phenotypes by altering gene expression. Our understanding of these variants is limited by sample sizes of current studies and by measurements of mRNA rather than protein abundance. We developed a…
The antibody repertoire of each individual is continuously updated by the evolutionary process of B cell receptor mutation and selection. It has recently become possible to gain detailed information concerning this process through…
We discuss a simple and powerful approach for the ab initio identification of cis-regulatory motifs involved in transcriptional regulation. The method we present integrates several elements: human-mouse comparison, statistical analysis of…
Transcriptional regulatory network inference methods have been studied for years. Most of them relie on complex mathematical and algorithmic concepts, making them hard to adapt, re-implement or integrate with other methods. To address this…
The birth of new genes is an important motor of evolutionary innovation. Whereas many new genes arise by gene duplication, others originate at genomic regions that do not contain any gene or gene copy. Some of these newly expressed genes…
Gene regulation is a dynamic process that connects genotype and phenotype. Given the difficulty of physically mapping mammalian gene circuitry, we require new computational methods to learn regulatory rules. Natural language is a valuable…
Understanding how molecular structure gives rise to odor perception remains a long-standing challenge, with ongoing debate over whether olfaction is primarily governed by molecular shape, vibrational properties, or their interplay at the…
The activation/repression of a given gene is typically regulated by multiple transcription factors (TFs) that bind at the gene regulatory region and recruit RNA polymerase (RNAP). The interactions between the promoter region and TFs and…
By integrating heterogeneous functional genomic datasets, we have developed a new framework for detecting combinatorial control of gene expression, which includes estimating transcription factor activities using a singular value…
Genetically identical cells in the same population can take on phenotypically variable states, leading to differentiated responses to external signals, such as nutrients and drug-induced stress. Many models and experiments have focused on a…
We consider integrative modeling of multiple gene networks and diverse genomic data, including protein-DNA binding, gene expression and DNA sequence data, to accurately identify the regulatory target genes of a transcription factor (TF).…
We develop a theoretical framework on the mechanism of combinatorial binding of transcription factors (TFs) with their specific binding sites on DNA. We consider three possible mechanisms viz. monomer, hetero-oligomer and coordinated…
Turing mechanisms can yield a large variety of patterns from noisy, homogenous initial conditions and have been proposed as patterning mechanism for many developmental processes. However, the molecular components that give rise to Turing…