Contribution of Transcription Factor Binding Site Motif Variants to Condition-Specific Gene Expression Patterns in Budding Yeast

It is now experimentally well known that variant sequences of a cis transcription factor binding site motif can contribute to differential regulation of genes. We characterize the relationship between motif variants and gene expression by analyzing expression microarray data and binding site predictions. To accomplish this, we statistically detect motif variants with effects that differ among environments. Such environmental specificity may be due to either affinity differences between variants or, more likely, differential interactions of TFs bound to these variants with cofactors, and with differential presence of cofactors across environments. We examine conservation of functional variants across four Saccharomyces species, and find that about a third of transcription factors have target genes that are differentially expressed in a condition-specific manner that is correlated with the nucleotide at variant motif positions. We find good correspondence between our results and some cases in the experimental literature (Reb1, Sum1, Mcm1, and Rap1). These results and growing consensus in the literature indicates that motif variants may often be functionally distinct, that this may be observed in genomic data, and that variants play an important role in condition-specific gene regulation

Low-Complexity Interactive Algorithms for Synchronization from Deletions, Insertions, and Substitutions

Consider two remote nodes having binary sequences $X$ and $Y$, respectively. $Y$ is an edited version of ${X}$, where the editing involves random deletions, insertions, and substitutions, possibly in bursts. The goal is for the node with $Y$ to reconstruct $X$ with minimal exchange of information over a noiseless link. The communication is measured in terms of both the total number of bits exchanged and the number of interactive rounds of communication. This paper focuses on the setting where the number of edits is $o(\tfrac{n}{\log n})$, where $n$ is the length of $X$. We first consider the case where the edits are a mixture of insertions and deletions (indels), and propose an interactive synchronization algorithm with near-optimal communication rate and average computational complexity of $O(n)$ arithmetic operations. The algorithm uses interaction to efficiently split the source sequence into substrings containing exactly one deletion or insertion. Each of these substrings is then synchronized using an optimal one-way synchronization code based on the single-deletion correcting channel codes of Varshamov and Tenengolts (VT codes). We then build on this synchronization algorithm in three different ways. First, it is modified to work with a single round of interaction. The reduction in the number of rounds comes at the expense of higher communication, which is quantified. Next, we present an extension to the practically important case where the insertions and deletions may occur in (potentially large) bursts. Finally, we show how to synchronize the sources to within a target Hamming distance. This feature can be used to differentiate between substitution and indel edits. In addition to theoretical performance bounds, we provide several validating simulation results for the proposed algorithms