Yeast TFBS identification and mutation impact assessment Demo

Introduction

This demo shows how the PWM are used to evalate the impact of mutations on transcription factor binding sites (TFBS). The data used here is:

1.PWMs for teh yeast TFs downloaded from [http://cisbp.ccbr.utoronto.ca/index.php] CIS-BP Database: Catalog of Inferred Sequence Binding Preferences.

2.The yeast genome sequence downloaded from [https://www.yeastgenome.org/] The Saccharomyces Genome Database (SGD).

3.The Bioconductor [https://bioconductor.org/packages/release/bioc/html/Biostrings.html] BioStrings R Package.

Loading libraries and data

## [1] "Number of loaded PWMs: 1440 - Length of loaded sequence: 230218bp."

Identify TFBS in the yeast chromosome 1

## [1] "Length of loaded sequence: 30000bp."

##     BS_Start PWM_Length Score    PWM_name BS_End BS_Sequence
##  1:     2638         10  5.02 M00110_2.00   2647  GCGGAGGAAA
##  2:     7762         10  5.51 M00110_2.00   7771  CCGGAGTAAT
##  3:     9328         10  5.16 M00110_2.00   9337  TCGGAAAACT
##  4:    10062         10  5.01 M00110_2.00  10071  ACGGATAACT
##  5:    11130         10  5.00 M00110_2.00  11139  TTGGATAAAT
##  6:    13556         10  5.08 M00110_2.00  13565  TCGGGCAATC
##  7:    14786         10  5.02 M00110_2.00  14795  AAGGAAAAAT
##  8:    16608         10  5.28 M00110_2.00  16617  ACGGGTAAAC
##  9:    17925         10  5.21 M00110_2.00  17934  TCGGGAAAAG
## 10:    18888         10  5.26 M00110_2.00  18897  TCGGAAATAT
## 11:    20517         10  5.15 M00110_2.00  20526  GCGGTAAATT
## 12:    21031         10  5.26 M00110_2.00  21040  ACGGGAAAAA
## 13:    21078         10  5.44 M00110_2.00  21087  TCGGAGAAAG
## 14:    23775         10  5.53 M00110_2.00  23784  ACGGTGAAAT
## 15:    29404         10  5.04 M00110_2.00  29413  ACGGTAAAAA

Plot the Sequence logo of this PWM

Sequence Logo for the PWM M00110_2.00.

Create mutants for each TFBS

## [1] "The wildtype sequences are mutated in 2 possition"

##     BS_Start PWM_Length Score    PWM_name BS_End BS_Sequence BS_Sequence_MT
##  1:     2638         10  5.02 M00110_2.00   2647  GCGGAGGAAA     GCTTAGGAAA
##  2:     7762         10  5.51 M00110_2.00   7771  CCGGAGTAAT     CCTTAGTAAT
##  3:     9328         10  5.16 M00110_2.00   9337  TCGGAAAACT     TCTTAAAACT
##  4:    10062         10  5.01 M00110_2.00  10071  ACGGATAACT     ACTTATAACT
##  5:    11130         10  5.00 M00110_2.00  11139  TTGGATAAAT     TTTTATAAAT
##  6:    13556         10  5.08 M00110_2.00  13565  TCGGGCAATC     TCTTGCAATC
##  7:    14786         10  5.02 M00110_2.00  14795  AAGGAAAAAT     AATTAAAAAT
##  8:    16608         10  5.28 M00110_2.00  16617  ACGGGTAAAC     ACTTGTAAAC
##  9:    17925         10  5.21 M00110_2.00  17934  TCGGGAAAAG     TCTTGAAAAG
## 10:    18888         10  5.26 M00110_2.00  18897  TCGGAAATAT     TCTTAAATAT
## 11:    20517         10  5.15 M00110_2.00  20526  GCGGTAAATT     GCTTTAAATT
## 12:    21031         10  5.26 M00110_2.00  21040  ACGGGAAAAA     ACTTGAAAAA
## 13:    21078         10  5.44 M00110_2.00  21087  TCGGAGAAAG     TCTTAGAAAG
## 14:    23775         10  5.53 M00110_2.00  23784  ACGGTGAAAT     ACTTTGAAAT
## 15:    29404         10  5.04 M00110_2.00  29413  ACGGTAAAAA     ACTTTAAAAA

Score the mutants

##     BS_Start PWM_Length Score    PWM_name BS_End BS_Sequence BS_Sequence_MT
##  1:     2638         10  5.02 M00110_2.00   2647  GCGGAGGAAA     GCTTAGGAAA
##  2:     7762         10  5.51 M00110_2.00   7771  CCGGAGTAAT     CCTTAGTAAT
##  3:     9328         10  5.16 M00110_2.00   9337  TCGGAAAACT     TCTTAAAACT
##  4:    10062         10  5.01 M00110_2.00  10071  ACGGATAACT     ACTTATAACT
##  5:    11130         10  5.00 M00110_2.00  11139  TTGGATAAAT     TTTTATAAAT
##  6:    13556         10  5.08 M00110_2.00  13565  TCGGGCAATC     TCTTGCAATC
##  7:    14786         10  5.02 M00110_2.00  14795  AAGGAAAAAT     AATTAAAAAT
##  8:    16608         10  5.28 M00110_2.00  16617  ACGGGTAAAC     ACTTGTAAAC
##  9:    17925         10  5.21 M00110_2.00  17934  TCGGGAAAAG     TCTTGAAAAG
## 10:    18888         10  5.26 M00110_2.00  18897  TCGGAAATAT     TCTTAAATAT
## 11:    20517         10  5.15 M00110_2.00  20526  GCGGTAAATT     GCTTTAAATT
## 12:    21031         10  5.26 M00110_2.00  21040  ACGGGAAAAA     ACTTGAAAAA
## 13:    21078         10  5.44 M00110_2.00  21087  TCGGAGAAAG     TCTTAGAAAG
## 14:    23775         10  5.53 M00110_2.00  23784  ACGGTGAAAT     ACTTTGAAAT
## 15:    29404         10  5.04 M00110_2.00  29413  ACGGTAAAAA     ACTTTAAAAA
##     MT_Score Delta_Score
##  1:     3.44         40%
##  2:     3.92         36%
##  3:     3.57         39%
##  4:     3.43         40%
##  5:     3.41         40%
##  6:     3.49         39%
##  7:     3.43         40%
##  8:     3.69         38%
##  9:     3.63         38%
## 10:     3.68         38%
## 11:     3.56         39%
## 12:     3.67         38%
## 13:     3.85         37%
## 14:     3.94         36%
## 15:     3.45         40%