相关论文: Computational and molecular dissection of an X-box…
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…
Transcription factors (TFs) exert their regulatory action by binding to DNA with specific sequence preferences. However, different TFs can partially share their binding sequences due to their common evolutionary origin. This `redundancy' of…
Predicting how genetic variation affects phenotypic outcomes at the organismal, cellular, and molecular levels requires deciphering the cis-regulatory code, the sequence rules by which non-coding regions regulate genes. In this perspective,…
Differences in transcriptional regulatory networks underlie much of the phenotypic variation observed across organisms. Changes to cis-regulatory elements are widely believed to be the predominant means by which regulatory networks evolve,…
Current biological AI models lack interpretability -- their internal representations do not correspond to biological relationships that researchers can examine. Understanding gene regulation requires models whose learned structure can be…
BACKGROUND: Transcriptional regulation is a key mechanism in the functioning of the cell, and is mostly effected through transcription factors binding to specific recognition motifs located upstream of the coding region of the regulated…
Despite recent advances in our ability to detect adaptive evolution involving the cis-regulation of gene expression, our knowledge of the molecular mechanisms underlying these adaptations has lagged far behind. Across all model organisms…
Genes are connected in complex networks of interactions where often the product of one gene is a transcription factor that alters the expression of another. Many of these networks are based on a few fundamental motifs leading to switches…
Summary: Macromolecular assembly vertebrates essential cellular processes, such as gene regulation and signal transduction. A major challenge for conventional computational methods to study these processes is tackling the exponential…
Genes are frequently regulated in complex manners, necessitating modelling approaches which go beyond simple (linear) gene-to-gene interactions and address the modularity of cis-regulatory regions and alternate transcription initiation…
Cells receive a wide variety of cellular and environmental signals, which must be processed combinatorially to generate specific and timely genetic responses. We present here a theoretical study on the combinatorial control and integration…
Promoters and enhancers are cis-regulatory elements (CREs), DNA sequences that bind transcription factor (TF) proteins to up- or down-regulate target genes. Decades-long efforts yielded TF-DNA interaction models that predict how strongly an…
Identity, response to external stimuli, and spatial architecture of a living system are central topics of molecular biology. Presently, they are largely seen as a result of the interplay between a gene repertoire and the regulatory…
Regulatory networks have evolved to allow gene expression to rapidly track changes in the environment as well as to buffer perturbations and maintain cellular homeostasis in the absence of change. Theoretical work and empirical…
Somatic mutations in cancer cells affect various genomic elements disrupting important cell functions. In particular, mutations in DNA binding sites recognized by transcription factors can alter regulator binding affinities and expression…
The principles underlying the architectural landscape of chromatin beyond the nucleosome level in living cells remains largely unknown despite its potential to play a role in mammalian gene regulation. We investigated the 3-dimensional…
The promise of discovering a functional blueprint of a cellular system from large-scale and high-throughput sequence and experimental data is predicated on the belief that the same top-down investigative approach that proved successful in…
Gene regulation is a complex process involving the role of several genomic elements which work in concert to drive spatio-temporal expression. The experimental characterization of gene regulatory elements is a very complex and…
In this work, we describe a computational framework for the genome-wide identification and characterization of mixed transcriptional/post-transcriptional regulatory circuits in humans. We concentrated in particular on feed-forward loops…
Gene regulation in Eukaryotes is mainly effected through transcription factors binding to rather short recognition motifs generally located upstream of the coding region. We present a novel computational method to identify regulatory…