Matlab Bioinformatics Toolkit Evaluation

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Matlab Bioinformatics Toolkit Evaluation

• Kanishka Bhutani

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What I expected ??

• Local/Global sequence alignments.
• Multiple sequence alignments.
• Choice of different scoring matrices (BLOSUM,
  PAM) for evaluation.
• Build Hidden Markov Models.
• Easily import sequences from databases (PFAM,PDB,
  Swissprot)

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What I found ??

• Most of the features.
• Bonus
• Microarray normalization tools.
• Microarray Visualization tools including box
  plots, heat maps.

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Any surprises ?

• No Multiple sequence alignments
• Avg./Std Dev. of hydrophobicity, solvent
  accessibility Command ?
• Proteinplot- GUI for protein structure
  analysis.
• Import your file to view, select parameters and
  display stats.

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What all I tried?

• Local alignment, Global alignment.
• For short sequences
• swalign(seq1,seq2)
• nwalign(seq1,seq2)
• seq1,seq2 AA or NT sequences.
• For imported long sequences
• Convert seq into a vector of integer values
• Commands nt2int, aa2int

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Pairwise Sequence alignment

• S getgenbank(NM_00001)
• M getgenbank(NM_00002)
• Output Header and a sequence.
• Knt2int(S.Sequence)
• Bnt2int(M.Sequence)
• sc,align nwalign K,B
• Alignment Score Aligned seq.

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Getting sequences V Easy !

• getgenbank Retrieve sequence information from
  Genbank database.
• getembl Retrieve seq. information from EMBL
  database.
• getpept Retrieve seq information from Genpept
  database.
• gethmmprof Get HMM from the PFAM database.

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Experiment

• hmmodel gethmmprof(PF00001)

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Visualization of model
Showhmmprof (hmmodel,scale,logodds)
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Get GPCR seqs

• S getgenbank (NM_024531)
• disp (S.Sequence)

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Alignment of the seqs

• var gethmmalignment
  (PF00001,type,seed)
• disp char(var.Header) char (var.Sequence)

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For GPCR Family C

• Similarly for diff families.
• Multiple aligned sequences retrieved.

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GUI proteinplot

• User friendly.
• Avg./ Std. dev values for
• Hydrophobicity.
• Secondary structure propensity (Alpha helices
  or beta strands)
• Accessibility (accessible and buried residues)

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Mglur1 plot (Proteinplot)
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Mglur1 results
Parameter Average () Std. Dev.()
Accessible residues 5.04 1.25
Buried residues 8.22 1.816
Alpha helix 0.89 0.1565
Beta sheet 0.97 0.1038
Hydrophobicity 3.01 0.9608
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Test a seq. with HMM

• Retrieve mglur1 from Genbank
• mgr getgenbank (NM_012407)
• glusequence mgr.sequence
• Test it with the HMM model class A
• a.sglu hmmprofalign (model A,
  glusequence,showscore,true)
• Score -203.53
• Seq

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Log odd score plot for best path
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Difficulties questions

• No multiple sequence alignment.
• Demos Not very helpful.
• Difficult to view the sequences as no disp
  command found.
• Bugs
• Storing huge sequences (GPCR A) in a file,
  parsing error.
• HMMprofdemo command abruptly stops and gives
  errors.
• Proteinplot (GUI) hangs the machine often.
• Verify the sequences using the HMM models ??
• Regular expression matches and highlighting those
  positions??

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Suggestions of experiment

• Given an unknown sample dataset of proteins,
  known dataset of proteins (known structural
  information).
• Utilize the BLMT to extract over expressed 4
  Grams in a protein sequence or a group of protein
  sequences from the known set.
• Use search for regular expression function in
  the Matlab toolkit to look for those 4 Grams in
  unknown proteins and hence predict their
  structure.