Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jul 1;21(3):625-639.
doi: 10.1093/biostatistics/kxy084.

MACPET: model-based analysis for ChIA-PET

Ioannis Vardaxis  1 , Finn Drabløs  2 , Morten B Rye  3 , Bo Henry Lindqvist  1
Affiliations

MACPET: model-based analysis for ChIA-PET

Ioannis Vardaxis et al. Biostatistics. .

Abstract

We present model-based analysis for ChIA-PET (MACPET), which analyzes paired-end read sequences provided by ChIA-PET for finding binding sites of a protein of interest. MACPET uses information from both tags of each PET and searches for binding sites in a two-dimensional space, while taking into account different noise levels in different genomic regions. MACPET shows favorable results compared with MACS in terms of motif occurrence and spatial resolution. Furthermore, significant binding sites discovered by MACPET are involved in a higher number of significant three-dimensional interactions than those discovered by MACS. MACPET is freely available on Bioconductor. ChIA-PET; MACPET; Model-based clustering; Paired-end tags; Peak-calling algorithm.

Keywords: ChIA-PET; MACPET; Model-based clustering; Paired-end tags; Peak-calling algorithm.

PubMed Disclaimer

Figures

Fig. 1.
Fig. 1.
Self-intra cut-off. Self-ligated and intra-chromosomal cut-offs for the three datasets. (a) ESR1 (MCF-7), (b) CTCF (MCF-7), and (c) CTCF (K562). The x-axis are the lengths of the PETs in log10 scale, while the y-axis is the frequency. The dashed line represents the cut-off point, where the self-ligated PETs are on its left side and the intra-chromosomal on its right.
Fig. 2.
Fig. 2.
De novo motif discovery. Comparison of motif discovery and spatial resolution between MACPET and MACS. The x-axis for all plots is the top formula image PBSs, sorted by significance in descending order for each method respectively. (a–c) Motif occurrence (y-axis) for (a) ESR1 (MCF-7), (b) CTCF (MCF-7), (c) CTCF (K562). (d–f) Spatial resolution (y-axis) for (d) ESR1 (MCF-7), (e) CTCF (MCF-7), (f) CTCF (K562).
Fig. 3.
Fig. 3.
Comparison of significant binding sites. (a–c) Venn diagrams of the significant PBSs from MACPET and MACS for (a) ESR1 (MCF-7), (b) CTCF (MCF-7), (c) CTCF (K562). (d–f) densities for the total number of tags in each significant PBSs from MACPET and MACS for (d) ESR1 (MCF-7), (e) CTCF (MCF-7), (f) CTCF (K562). The x-axis is the total tags in log scale and the y-axis is the density of the total tags. (g–i) densities for the sizes of the significant PBSs from MACPET and MACS for (g) ESR1 (MCF-7), (h) CTCF (MCF-7), (i) CTCF (K562). The x-axis is the sizes of the significant PBSs and the y-axis is their density.
Fig. 4.
Fig. 4.
Comparison for MANGO interactions. Comparison of MANGO interaction results between significant PBSs from MACPET (peaks’ FDR formula image) and MACS (peaks’ FDR formula image, FDR formula image and top formula image most significant peaks), for different PBSs extension windows. For all the plots, the x-axis is the number of bp. Each PBS interval was extended from either side before running MANGO. (a–c) Total significant interactions (y-axis) for (a) ESR1 (MCF-7), (b) CTCF (MCF-7), (c) CTCF (K562). (d–f) Proportion of significant PBSs involved in significant interactions (y-axis) for (d) ESR1 (MCF-7), (e) CTCF (MCF-7), (f) CTCF (K562).
Fig. 5.
Fig. 5.
Comparison for MANGO interactions of formula image bp window extension. (a–c) Venn diagrams from significant interactions for a formula image bp extension window for the significant PBSs from MACPET and MACS for (a) ESR1 (MCF-7), (b) CTCF (MCF-7), (c) CTCF (K562). (d–f) Density plots for the distances of the significant intra-chromosomal interactions from MACPET and MACS for (d) ESR1 (MCF-7), (e) CTCF (MCF-7), (f) CTCF (K562). The x-axis is the sizes of the intra-chromosomal interactions and the y-axis is their density.
See this image and copyright information in PMC

References

    1. Arslan, O. and Genç, A. İ. (2009). The SGT as the scale mixture of a skew exponential power distribution and its applications in robust estimation. Statistics 43, 481–498.
    1. Benjamini, Y. and Hochberg, Y. (1995). Controlling the false discovery rate: a practical and powerful approach to multiple testing. Journal of the Royal Statistical Society Series B (Methodological) 57, 289–300.
    1. Buenrostro, J. D., Giresi, P. G., Zaba, L. C., Chang, H. Y. and Greenleaf, W. J. (2013). Transposition of native chromatin for multimodal regulatory analysis and personal epigenomics. Nature Methods 10, 1213–1218. - PMC - PubMed
    1. Chiu, K., Wong, C.-H., Chen, Q., Ariyaratne, P., Ooi, H., Wei, C.-L., Sung, W.-K. and Ruan, Y. (2006). PET-Tool: a software suite for comprehensive processing and managing of Paired-End diTag (PET) sequence data. BMC Bioinformatics 7, 390. - PMC - PubMed
    1. Dekker, J., Rippe, K., Dekker, M. and Kleckner, N. (2002). Capturing chromosome conformation. Science 295, 1306–1311. - PubMed

Publication types

LinkOut - more resources