DAME finder : A package to detect changes in allele-specific - - PowerPoint PPT Presentation

▶
dame finder a package to detect changes in allele
SMART_READER_LITE
LIVE PREVIEW

DAME finder : A package to detect changes in allele-specific - - PowerPoint PPT Presentation

Jan 30, 2024 119 likes •373 views

DAME finder : A package to detect changes in allele-specific methylation Stephany Orjuela Len EuroBioc December 2019 Stands for D A ME Stands for Differential A ME Stands for Differential Allele-specific ME Stands for Differential

slide-1
SLIDE 1

DAMEfinder: A package to detect changes in allele-specific methylation

Stephany Orjuela León

EuroBioc December 2019

slide-2
SLIDE 2

Stands for

D A ME

slide-3
SLIDE 3

Stands for

Differential A ME

slide-4
SLIDE 4

Stands for

Differential Allele-specific ME

slide-5
SLIDE 5

Stands for

Differential Allele-specific MEthylated region

slide-6
SLIDE 6

The world of differential Bioconductor

slide-7
SLIDE 7

What is allele-specific methylation? (in humans at least)

Simplified biology:

slide-8
SLIDE 8

What is allele-specific methylation? (in humans at least)

In the reads (from Bisulfite-seq): Simplified biology:

SNP = single nucleotide polymorphism

slide-9
SLIDE 9

What is allele-specific methylation? (in humans at least)

In the reads (from Bisulfite-seq): Simplified biology:

slide-10
SLIDE 10

When do changes in allele-specific methylation occur?

slide-11
SLIDE 11

An example in colorectal cancer

“...loss of the normal parent of

  • rigin dependent gene silencing...”

Cui et. al., Cancer Research. 2002

When do changes in allele-specific methylation occur?

slide-12
SLIDE 12

What does the package do?

1. Detect ASM for each sample

calc_asm(sampleList, beta = 0.5, a = 0.2, transform = modulus_sqrt, coverage = 5, verbose = TRUE) r a n g e d

slide-13
SLIDE 13
  • 2. Summarize ASM change with a moderated t-stat

r a n g e d

slide-14
SLIDE 14
  • 2. Summarize ASM change with a moderated t-stat

r a n g e d

Group A Group B

slide-15
SLIDE 15
  • 3. Scan for regions of consistent change

bumphunter find_dames(SumExp, design, coef = 2, contrast = NULL, smooth = TRUE, Q = 0.5, pvalAssign = "simes", maxGap = 20, verbose = TRUE, maxPerms = 10, method = "ls", trend = FALSE, ...)

slide-16
SLIDE 16
  • 4. Visualization

Plot reads overlapping a SNP (all or a random subset of the reads)

Sample1 Sample2

methyl_circle_plot (snp, vcfFile, bamFile, refFile, dame = NULL, letterSize = 2.5, pointSize = 3, sampleReads = FALSE, numReads = 20)

slide-17
SLIDE 17

Sorted by methylation

Plot (random subset of) reads in a region

Sample1 Sample2 methyl_circle_plotCpG (cpgsite, bamFile, refFile, pointSize = 3, dame = NULL,

  • rder = FALSE,

sampleReads = FALSE, numReads = 20)

slide-18
SLIDE 18

Plot summary of scores

dame_track(dame, window = 0, derASM = snpASM, ASM = tupleASM, colvec = color, plotSNP = TRUE)

slide-19
SLIDE 19

To summarize

1. DAMEfinder detects allele-specific methylation from BS-seq data

slide-20
SLIDE 20

To summarize

1. DAMEfinder detects allele-specific methylation from BS-seq data 2. Allele-specific methylation can be SNP-based, or not

slide-21
SLIDE 21

To summarize

1. DAMEfinder detects allele-specific methylation from BS-seq data 2. Allele-specific methylation can be SNP-based, or not 3. The package screens for regions of change in allele-specificity

slide-22
SLIDE 22

To summarize

1. DAMEfinder detects allele-specific methylation from BS-seq data 2. Allele-specific methylation can be SNP-based, or not 3. The package screens for regions of change in allele-specificity 4. It makes region-wise plots

slide-23
SLIDE 23

https://github.com/markrobinsonuzh/DAMEfinder

slide-24
SLIDE 24

Acknowledgements

The Robinson lab: Mark Robinson, Dania Machlab (from the previous talk) The Marra lab: Giancarlo Marra, Hannah Parker