Kismeth: analyzer of plant methylation states through bisulfite sequencing.
BACKGROUND
There is great interest in probing the temporal and spatial patterns of cytosine methylation states in genomes of a variety of organisms. It is hoped that this will shed light on the biological roles of DNA methylation in the epigenetic control of gene expression. Bisulfite sequencing refers to the treatment of isolated DNA with sodium bisulfite to convert unmethylated cytosine to uracil, with PCR converting the uracil to thymidine followed by sequencing of the resultant DNA to detect DNA methylation. For the study of DNA methylation, plants provide an excellent model system, since they can tolerate major changes in their DNA methylation patterns and have long been studied for the effects of DNA methylation on transposons and epimutations. However, in contrast to the situation in animals, there aren't many tools that analyze bisulfite data in plants, which can exhibit methylation of cytosines in a variety of sequence contexts (CG, CHG, and CHH).


RESULTS
Kismeth http://katahdin.mssm.edu/kismeth is a web-based tool for bisulfite sequencing analysis. Kismeth was designed to be used with plants, since it considers potential cytosine methylation in any sequence context (CG, CHG, and CHH). It provides a tool for the design of bisulfite primers as well as several tools for the analysis of the bisulfite sequencing results. Kismeth is not limited to data from plants, as it can be used with data from any species.


CONCLUSIONS
Kismeth simplifies bisulfite sequencing analysis. It is the only publicly available tool for the design of bisulfite primers for plants, and one of the few tools for the analysis of methylation patterns in plants. It facilitates analysis at both global and local scales, demonstrated in the examples cited in the text, allowing dissection of the genetic pathways involved in DNA methylation. Kismeth can also be used to study methylation states in different tissues and disease cells compared to a reference sequence.
Gruntman
Eyal
E
gruntman@cshl.edu
Qi
Yijun
Y
Slotkin
R Keith
RK
Roeder
Ted
T
Martienssen
Robert A
RA
Sachidanandam
Ravi
R
D000465:Algorithms; D001483:Base Sequence; D019175:DNA Methylation; D018744:DNA, Plant / Q000737:chemistry* / Q000235:genetics*; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA / Q000379:methods*; D012984:Software; D013447:Sulfites / Q000737:chemistry*
D018744:DNA, Plant; D013447:Sulfites; C009279:sodium bisulfite
Nat Rev Genet. 2002 Jun;3(6):415-28
12042769
Annu Rev Plant Biol. 2004;55:41-68
15725056
Genes Dev. 2001 Mar 1;15(5):591-602
11238379
Nature. 2001 May 10;411(6834):212-4
11346800
Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1827-31
1542678
Nature. 2004 Jul 22;430(6998):471-6
15269773
Science. 2003 Jan 31;299(5607):716-9
12522258
Cancer Res. 2007 Sep 15;67(18):8511-8
17875690
Proc Natl Acad Sci U S A. 2002 Dec 10;99 Suppl 4:16491-8
12151602
Nat Rev Genet. 2005 May;6(5):351-60
15861207
Plant Cell. 2006 Jun;18(6):1360-72
16648367
Plant Cell. 2006 Apr;18(4):805-14
16531498
Plant J. 2007 Aug;51(3):526-36
17559516
Genome Res. 1998 Mar;8(3):175-85
9521921
Nucleic Acids Res. 1994 Aug 11;22(15):2990-7
8065911
Genes Dev. 2002 Jan 1;16(1):6-21
11782440