DNase-seq allows nucleotide-level identification of transcription factor binding sites on the basis of a computational search of footprint-like DNase I cleavage patterns on the DNA. Frequently in high-throughput methods, experimental artifacts such as DNase I cleavage bias affect the computational analysis of DNase-seq experiments. Here we performed a comprehensive and systematic study on the performance of computational footprinting methods. We evaluated ten footprinting methods in a panel of DNase-seq experiments for their ability to recover cell-specific transcription factor binding sites. We show that three methods--HINT, DNase2TF and PIQ--consistently outperformed the other evaluated methods and that correcting the DNase-seq signal for experimental artifacts significantly improved the accuracy of computational footprints. We also propose a score that can be used to detect footprints arising from transcription factors with potentially short residence times.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/nmeth.3772 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Carbon footprint of private dental clinics in Egypt: a cross-sectional study.
BMC Oral Health
January 2025
Afrone Network, Faculty of Dentistry, Alexandria University, Alexandria, Egypt.
Background: Climate change is a global challenge, caused by increasing greenhouse gas (GHG) emissions. Dental clinical practice contributes to these emissions through patient and staff travel, waste, energy and water consumption and procurement. Carbon footprinting quantifies GHG emissions.
View Article and Find Full Text PDFIdentification of G-quadruplex nucleic acid structures by high-throughput sequencing: A review.
Int J Biol Macromol
January 2025
School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China; Smart Medical Innovation Technology Center, Guangdong University of Technology, Guangzhou 510006, China. Electronic address:
G-quadruplexes (G4s) are non-canonical nucleic acid secondary structures formed by guanine-rich DNA or RNA sequences. These structures play pivotal roles in cellular processes, including DNA replication, transcription, RNA splicing, and protein translation. High-throughput sequencing has significantly advanced the study of G4s by enabling genome-wide mapping and detailed characterization.
View Article and Find Full Text PDFMass Spectrometry-Based Protein Footprinting for Protein Structure Characterization.
Acc Chem Res
January 2025
Department of Chemistry, Washington University, St. Louis, Missouri 63130, United States.
ConspectusProtein higher-order structure (HOS) is key to biological function because the mechanisms of protein machinery are encoded in protein three-dimensional structures. Mass spectrometry (MS)-based protein footprinting is advancing protein structure characterization by mapping solvent-accessible regions of proteins and changes in H-bonding, thereby providing higher order structural information. Footprinting provides insights into protein dynamics, conformational changes, and interactions, and when conducted in a differential way, can readily reveal those regions that undergo conformational change in response to perturbations such as ligand binding, mutation, thermal stress, or aggregation.
View Article and Find Full Text PDFEnabling simultaneous photoluminescence spectroscopy and X-ray footprinting mass spectrometry to study protein conformation and interactions.
Anal Methods
January 2025
Molecular Foundry Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
X-ray footprinting mass spectrometry (XFMS) is a structural biology method that uses broadband X-rays for hydroxyl radical labeling to map protein interactions and conformation in solution. However, while XFMS alone provides important structural information on biomolecules, as we move into the era of the interactome, hybrid methods are becoming increasingly necessary to gain a comprehensive understanding of protein complexes and interactions. Toward this end, we report the development of the first synergetic application of inline and real-time fluorescent spectroscopy at the Advanced Light Source's XFMS facility to study local protein interactions and global conformational changes simultaneously.
View Article and Find Full Text PDFChromatinHD connects single-cell DNA accessibility and conformation to gene expression through scale-adaptive machine learning.
Nat Commun
January 2025
Laboratory of Systems Biology and Genetics, Institute of Bio-engineering and Global Health Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
Gene regulation is inherently multiscale, but scale-adaptive machine learning methods that fully exploit this property in single-nucleus accessibility data are still lacking. Here, we develop ChromatinHD, a pair of scale-adaptive models that uses the raw accessibility data, without peak-calling or windows, to link regions to gene expression and determine differentially accessible chromatin. We show how ChromatinHD consistently outperforms existing peak and window-based approaches and find that this is due to a large number of uniquely captured, functional accessibility changes within and outside of putative cis-regulatory regions.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!