A Specific Methylation Analysis and Report Tool 1.0 for BS-Seq data

New version of SMART (2.0) is available now!


It is known that DNA methylation plays important roles in regulation of cell development and differentiation. DNA methylation/unmethylation mechanisms are common in all tissue/cell. However, different cell types with the same genome have different methylomes. Recently, high-throughput sequencing combining bisulfite treatment (Bisulfite -Seq) have been used to generate DNA methylomes from a wide range of human tissue/cell types at a genome-wide perspective. To characterize the genome regions that consist of continuous CpGs with similar methylation specificity, we developed the Specific Methylation Analysis and Report Tool (SMART) based on the quantified methylation specificity, Euclidean distance and similarity entropy, for identifying and characterizing sets of genome segments comprising continuous CpGs with similar methylation specificities. For a given set of multiple methylomes profiled using BS-Seq, entropy-based procedures facilitated the quantification of methylation specificity for each CpG and the determination of the Euclidean distance and similar entropy for each pair of neighboring CpGs. Subsequently, continuous scanning based on these quantified parameters segments the genome into primary segments comprising CpG sites with high methylation similarities across all cell types. Further, the primary segments in close proximity and sharing similar methylation patterns were merged into larger segments of different types, including high specificity (HighSpe), intermediate specificity (InterSpe) and low specificity (LowSpe) segments. Eventually, the High/InterSpe segments with specific hypo-/hypermethylation in the minority of cell types, cell-type-specific hypomethylation marks (HypoMarks) and cell-type-specific hypermethylation marks (HyperMarks), were identified using a statistical method. To facilitate the mining of methylation marks (MethyMarks) across cell types and species, all algorithms used in this procedure were integrated into a Specific Methylation Analysis and Report Tool (SMART), which is also available at

Now, the newest version is version 1.4.2



SMART is developed based on Shannon entropy and written in Python by Hongbo Liu (


Source Code

The source code of SMART is stored on PyPI - the Python Package Index which is a repository of software for the Python programming language. To use SMART package from this index either "pip install SMART-BS-Seq" (get pip) or download, unpack and "python install" it.


Cite us

If you use this tool, please cite the paper

Hongbo Liu et al. Systematic identification and annotation of human methylation marks based on bisulfite sequencing methylomes reveals distinct roles of cell type-specific hypomethylation in the regulation of cell identity genes Nucleic Acids Res: 2016 ,44(1) ,75-94.