Bioinformatics: A Personal Perspective

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BioinformaticsA Personal Perspective

• Arthur W. Chou
• Spring 2005

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There once lived a man who learned how to slay
dragons and give all he possessed to mastering
the art. After three year he was fully prepared
but, alas, he found no opportunity To practice
his skills. - Zhuan Zhi
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As a result he began To teach how to slay
dragons.
- Rene Thom
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(No Transcript)
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Sequence Analysis of gp120 in HIV-1 Virus

• Highly variable levels of N-linked
  glycosylation on the V1 loop of HIV-1 envelope
  glycoproteins and their relationship to the
  immunogenicity of HIV Env of primary viral
  isolates
• by
• Shixia Wang, Innocent Mboudjeka, Zuhu Huang,
  Siyuan Shen, Jonathan Tanguay, Arthur Chou,
• Te-Hui Wu, and Shan Lu
• ( submitted to Journal of Virology )

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HIV particle and genome
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HIV vaccines approaches
recombinant protein (gp120)
synthetic peptides (V3)
naked DNA
live-recombinant vectors (viral, bacterial)
whole-inactivated virus
live-attenuated virus
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HIV env genetic subtypes
Adapted from J. Mullins
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HIV-1 Envelope Glycoprotein Domains
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Tertiary structure of HIV-1 gp120 protein
HIV sequences-2.ppt
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Observation

• The lengths of the V1 loop vary with the number
  of N-glycosylation sites i.e, the longer the
  V1 loop, the more the number of sites.
• V1 loop
• Length No. of Glycosylation sites
• 15 - 25 2 - 4
• 26 - 45 4 - 7

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Questions

• Does this correlation between the length of the
  sequences and the number of glycosylation sites
  only occur in V1?
• How are the glycosylation sites distributed
  throughout the sequences?

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Results of Sequence Analysis

• This high correlation rarely occurs at other
  places the average number of glycosylation
  sites for any stretch of length 45 is 2.5 .
• Analysis of the distribution of Glycosylation
  sites show that they are mostly concentrated on
  the V1 loop.

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Results of the paper

• Mutated Env antigen with selected removal of
  N-glycosylation sites at the tip of V1 loop on
  one of the primary HIV-1 Env, 92US715, induced
  higher antibody responses against the autologous
  HIV virus.
• Contribution These data improve our
  understanding on the structure-function
  relationship of HIV-1 Env antigens, and
  facilitate better design of HIV vaccines with the
  aim of inducing broad neutralizing antibody
  responses.

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Algorithm

• Distance-Based method
• Dynamic Programming

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Distance Matrix of Glycosylation Sites

• A1 length 465
• N-Glycosylation sites
• 85
• 129 134 141 145 173 184
• 221 228 249 263 282 288 325
• 341 371 377 383 388 389 393
• 430 442 443
• s1 85, s2 129, s3 134, etc.
• Distance Matrix D D i, j sj -
  si

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The Distance Matrix D i, j sj - si
j

• i 1 2 3 4 . . . n
• 1 0 44 49 56
• 2 - 0 5 12
• 3 - - 0 7
• 4 - - - 0
• .
• .
• n

Fast Search Algorithm Dynamic Programming
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