Promoter Panel

1
Promoter Panel

• Review

2
Background related Promoter

• In genetics, a promoter is a DNA sequence that
  enables a gene to be transcribed. It may be very
  long and may have multiple elements.
• In geWorkBench, Promoter Panel is used to
  discover potential transcription factor binding
  sites, based on known transcription factor
  binding profiles.

3
Background Contd

• Available Transcription factor binding profile
  databases
• Transfac most complete but commercial, about
  700 matrices
• JASPAR open source. Now it has 3 categories
• JASPAR CORE 123 profiles
• JASPAR PHYLOFACTS 174 profiles
• JASPAR FAM familial profiles based on CORE.
• geWorkbench uses 108 matrices from an old
  versioned JASPAR CORE.

4
Background Contd

For sequence AAAGTA SCORE 21/21 21/21 21/21
21/21 8/21 6/21 0.108
5
Algorithm

• Normalize the matrix, P(i) will be gt 0.
• The formula for the score is very simple
  SlogP(i)
• Create a background sequence, two ways to create
  background sequence.
• Scan the background sequence to set up the
  threshold. For a length of 1K background
  sequence, you can get about 1000-Matrix.length
  scores. The threshold is based on the P-value.
  For example, for P-Value 0.05. The threshold is
  the lowest score for the top 5 scores.
• Scan the input sequence and report hits above the
  threshold.
• Report results
• In summary, The result is very stringent.
  Bonferroni Correction is used. P-Value is really
  PValue/1K. Best for detecting enrichment of some
  patterns.

6
Issues - Programmatic

• The algorithm is not very efficient. For every
  TF, one scan of the background and input sequence
  is required. Most of the time is spent on
  scanning background sequences.
• Do all tests on Protein sequences. Stop button
  doesnt work.
• Different species.
• The 13K background sequence? Different programs
  use different background sequence.
• Module discovery is not correctly programmed?
• Too stringent for finding hits, good for checking
  enrichments.
• Miss All Sequences button.
• What can we do after we get the patterns? Save
  result do not work properly.

7
Issues - GUI

• The logo is in poor quality. It should provide
  more information and should be in a separate
  panel.
• Separate parameters and results.
• The TFBS should be marked with direction, 5 or
  3.
• Use updated Sequence Panel.
• No Image snapshot function.

8
Proposed fixes

• Update JASPAR Profiles
• Provide more information about the matrix. Use
  JASPAR Logos for JASPAR CORE, Use enoLogos
  instead of BioJava for user defined matrix to get
  high quality pictures.
• Scan once only.
• Get more information about 13K sequences. Cache
  the threshold for 13K.
• Change the GUI.