Evolutionary exploitation of miRNA by phylogeny tree construction

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Evolutionary exploitation of miRNA by phylogeny
tree construction

• Presentation Shaojun Tang Shizhao Zhou
• Genetics Institute, College of Medicine,
  University of Florida
• Computer information and science engineering,
  University of Florida
• Mentor Tamer Kahveci

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Outline

• Part I What and why miRNA ?
• Part II Gene regulation governed by
  transcription binding and miRNA targeting.
• Part III Phylogeny tree construction of miRNA
  from different organism.
• Part IV Multiply sequence alignment analysis to
  identify evolutionary conserved miRNAs.

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Part I What and why miRNA.

• What is miRNA.
• Ribonucleic acid(RNA) molecules of about
  2123 nucleotides long, which regulation gene
  expression.

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• Function of miRNA
• 1 Mature miRNA molecules are partially
  complementary to one or more message RNA (mRNA)
  molecules, which down-regulate gene expression
• 2 miRNA regulation of gene expression are
  associated with many disease and even cancer.

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• Current research of miRNA
• 1 more than 700 miRNAs are identified in
  humans
• 2 miRNA regulation of gene transcription is
  important, but poorly understood and addressed.
• 3 miRNA can be a powerful tool in helping
  solve many disease or cancer in human.

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Part II Gene regulation governed by transcription
factor and miRNA

• Transcription factor (sequence-specific DNA
  binding factor)
• Specific factors such as protein, that binds to
  particular DNA sequence and thereby controls the
  gene transcription from DNA to RNA.

Transcription factor
Gene
Binding site
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Methods

• 1 Database of transcription factor, human
  pathway genes, miRNA targets.
• 2 Calculate occurrence of transcription
  factor(the gene controlling factors) and
  downstream miRNA target sites.

Pathway A
TF-k
TF-m
TAR-i
Gene-1
Pathway TF TAR
A k 2 m1 i2 J1
B ---- -----
- - - - -
TAR-i
TF-k
TAR-j
Gene-n
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Results

• 871 pathways each associated with a group(20) of
  high-frequency transcription factor and miRNA
  targets.
• Important for study pathway gene regulation and
  disease.

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Part III Phylogeny tree construction

• Data for analysis
• All available miRNA sequences from Human,
  mice, drosophila and virus.
• Algorithm
• Dynamic program to generate scoring-matrix,
  follow by implementing UPGMA method to cluster
  miRNA sequences.
• Methods
• Using two approaches for self-verification
  and more powerful evidence.

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Method implementation-1

• Forward-construction (low gt high)

Overlap miRNAs
Cluster of miRNA
Individual miRNA
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• Finding pairwise clusters of miRNA

individual miRNAs
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1
1
5
2
2
----
3
4
Cluster of miRNAs
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Closely related miRNA cluster
Cluster of miRNAs
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Method implementation-2

• Backward-construction

Individual miRNA
miRNA clusters from UPGMA
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Data

• Organisms
• KSHV Kaposi's sarcoma-associated
  herpesvirus
• EBV Epstein-Barr virus
• Dm Drosophila melanogaster
• Mm Mus_musculus
• Hs Homo_Sapiens
• Groups of phylogeny tress
• 1 KSHV gt Dm gt Hs
• 2 Ebv gt Dm gt Mm

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• Results of a Single group
• 1) Forward construction
• 3 tables from Edit(0, 1, 1) (0, 1 3)
  Percentage
• 2) Backward construction
• 3 tables from Edit(0, 1, 1) (0, 1 3)
  Percentage

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Conclusion

• 1 The association of transcription factor
  binding site and miRNA targets given the pathway
  can provide useful information for research
  related to pathways.
• 2 The UPGMA construction of phylogeny tree may
  provide useful information for clustering
  evolutionary conserved genes in any given
  organism,.
• 3 while our two methods of miRNA pairwise
  construction among organism may shield light on
  future research in miRNA evolution, regulation
  and function.

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Thank you