Information Technology As A CATALYST in Basic Biological Research

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Information Technology As A CATALYST in Basic
Biological Research

• Sudha Bhattacharya
• J.N.U.
• New Delhi

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• Mining of gene Sequence Data
• Pattern finding in DNA

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Specific Example

• The Retrotransposons in Entamoeba histolytica
• genome

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Retrotransposons

• Mobile DNA elements
• Some insert in a sequence specific manner
• Others are widely distributed
• Can disrupt the function of genes resulting in
  diseases

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What Information can Bioinformatics provide?

• I. Defining the element.
• II. Where is the element located in the genome.
• III. Pattern Finding in preinsertion sites.

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I. Defining the Element

• Its size
• Copy number in the genome
• Are all copies full length?
• Are all copies functional?
• To which group this element belongs (DNA
  transposon, LTR retrotransposon, non LTR
  retrotransposon)

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Empty site
Post insertion
(could be truncated)

• Defining the end points
• Of the Element by
• Sequence alignment
• Constructing a consensus
• Sequence with no
• Mutation
• Type of Element- Deduced
• by BLAST search, using the
• sequence of reconstructed
• element

Reconstructed consensus element
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Consensus structures of EhLINEs/SINEs
Bakre Abhijeet
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Genomic abundance of full-length and truncated
copies of EhLINEs and EhSINEs.
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II. Where is the element located in the genome.

• Element Analyzer (ELAN) a tool that searches
  the genome and locates all the elements.

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ELAN
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Occurrence of genes and other elements near
EhLINEs/SINEs
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(No Transcript)
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Genes located downstream of EhLINE 1
From analysis of both genes upstream and
downstream, it is clear that EhLINE 1 has invaded
the genome widely
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III. Pattern Finding

• Although the element inserts in many locations,
  it has some preferences.
• What are these?

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Preferred sites

• The sites that are preferred by Endonuclease for
  nicking (GCATT)
• Amongst these, the sites that have preferred
  structure

GCATT
GCATT
? ?
? ?
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DNA structure criteria tested based on
dinucleotide frequencies

• Thymine Excess
• Bendability
• Propeller Twist
• Stacking Energy
• Free Energy
• DNA Denaturation Energy
• Protein induced deformability
• Nucleosome positioning

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Computational analysis of preinsertion loci
(b)
(a)
(d)
(c)
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Conclusion

• EhLINEs/SINEs insert in a rigid region that can
  melt easily and is 10-35 nucleotides upstream of
  the preferred EN sequence (GCATT)

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DNA SCANNER
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Identification of insertion hot spots for non LTR
retrotransposons computational and
biochemicalapplication to Entamoeba histolytica
Nucleic Acids Research, 2006, Vol. 00, No. 00
112 doi10.1093/nar/gkl710

• Prabhat K. Mandal3, Kamal Rawal1, Ram Ramaswamy
  1,2, Alok Bhattacharya 1,3 and Sudha
  Bhattacharya

School of Environmental Sciences, Jawaharlal
Nehru University, New Mehrauli Road, New Delhi
110 067, India, 1School of Information
Technology, Jawaharlal Nehru University, New
Delhi 110 067, India, 2School of
Physical Sciences, Jawaharlal Nehru University,
New Delhi 110 067, India and 3School of Life
Sciences, Jawaharlal Nehru University, New Delhi
110 067, India Received June 26, 2006 Revised
August 22, 2006 Accepted September 14, 2006
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THANKS!