Kyoto University · 생화학·유전·분자생물학
알렉시스 반덴본 교수의 연구실은 단일세포 유전자 발현 데이터 분석과 면역세포의 전사 조절 네트워크를 중심으로, 유전자 발현의 공간적 배치와 조절 요소 간의 상호작용을 규명하는 데 초점을 맞추고 있습니다. 특히 단일세포 시퀀싱 데이터에서 클러스터링에 의존하지 않는 DEG 예측 기법과 배치효과를 보정한 면역세포 전사체 데이터베이스 구축을 통해 생물학적 신뢰도를 높이는 데 기여하고 있습니다. 또한 전사 인자, 히스톤 변형, 프로모터 구조 등 전사 조절 메커니즘의 계층적 동역학을 체계적으로 분석하고 있습니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
A common analysis of single-cell sequencing data includes clustering of cells and identifying differentially expressed genes (DEGs). How cell clusters are defined has important consequences for downstream analyses and the interpretation of results, but is often not straightforward. To address this difficulty, we present singleCellHaystack, a method that enables the prediction of DEGs without relying on explicit clustering of cells. Our method uses Kullback-Leibler divergence to find genes that a
High-throughput gene expression data are one of the primary resources for exploring complex intracellular dynamics in modern biology. The integration of large amounts of public data may allow us to examine general dynamical relationships between regulators and target genes. However, obstacles for such analyses are study-specific biases or batch effects in the original data. Here we present Immuno-Navigator, a batch-corrected gene expression and coexpression database for 24 cell types of the mous
Sets of genes expressed in the same tissue are believed to be under the regulation of a similar set of transcription factors, and can thus be assumed to contain similar structural patterns in their regulatory regions. Here we present a study of the structural patterns in promoters of genes expressed specifically in 26 human and 34 mouse tissues. For each tissue we constructed promoter structure models, taking into account presences of motifs, their positioning to the transcription start site, an
The importance of transcription factors (TFs) and epigenetic modifications in the control of gene expression is widely accepted. However, causal relationships between changes in TF binding, histone modifications, and gene expression during the response to extracellular stimuli are not well understood. Here, we analyze the ordering of these events on a genome-wide scale in dendritic cells in response to lipopolysaccharide (LPS) stimulation. Using a ChIP-seq time series dataset, we find that the L
Toll-like receptor (TLR) signaling pathways constitute an evolutionarily conserved host defense system that protects against a broad range of infectious agents. Modeling of TLR signaling has been carried out at several levels. Structural models of TLRs and their adaptors, which utilize a small number of structural domains to recognize a diverse range of pathogens, provide a starting point for understanding how pathogens are recognized and signaling events initiated. Various experimental and comp
A key point for accurate prediction of gene co-expression is the collection of many samples. However, paying attention to data normalization, batch effects, and the measure of correlation can significantly improve the quality of co-expression estimates.
Both computational and experimental results indicate that the proposed method can clarify TF interactions that could not be observed by currently available prediction methods.
Transcriptional regulation is the first level of regulation of gene expression and is therefore a major topic in computational biology. Genes with similar expression patterns can be assumed to be co-regulated at the transcriptional level by promoter sequences with a similar structure. Current approaches for modeling shared regulatory features tend to focus mainly on clustering of cis-regulatory sites. Here we introduce a Markov chain-based promoter structure model that uses both shared motifs an
With the growing complexity of single-cell and spatial genomics data, there is an increasing importance of unbiased and efficient exploratory data analysis tools. One common exploratory data analysis step is the prediction of genes with different levels of activity in a subset of cells or locations inside a tissue. We previously developed singleCellHaystack, a method for predicting differentially expressed genes from single-cell transcriptome data, without relying on comparisons between clusters
The results presented in this study reveal the complexity and dynamics of TF- enhancer binding before and after stimulation in myeloid APCs.
Our approach can be used to suggest testable hypotheses for wet-lab experiments. It has potential for future analyses, such as the prediction of weaker binding sites. An online application of our approach, called LocaMo Finder (Local Motif Finder), is available at http://sysimm.ifrec.osaka-u.ac.jp/tfbs/locamo/.
Regulation of transcription is controlled by sets of transcription factors binding specific sites in the regulatory regions of genes. It is therefore believed that regulatory regions driving similar expression profiles share some common structural features. We here introduce a computational approach for finding a small set of rules describing the presence and positioning of motifs in a set of promoter sequences. This rule set is subsequently used for finding promoters that drive similar expressi
ABSTRACT With the growing complexity of single-cell and spatial genomics data, there is an increasing importance of unbiased and efficient exploratory data analysis tools. One common exploratory data analysis step is the prediction of genes with different levels of activity in a subset of cells or locations inside a tissue. We previously developed singleCellHaystack, a method for predicting differentially expressed genes from single-cell transcriptome data, without relying on clustering of cells
Abstract Background The importance of transcription factors (TFs) and epigenetic modifications in the control of gene expression is widely accepted. However, causal relationships between changes in TF binding, histone modifications, and gene expression during the response to extracellular stimuli are not well understood. Here, we analyzed the ordering of these events on a genome-wide scale in dendritic cells (DCs) in response to lipopolysaccharide (LPS) stimulation. Results Using a ChIP-seq time