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Towards a reliable objective function for multiple sequence alignments.

J D Thompson1, F Plewniak, R Ripp

  • 1Laboratoire de Biologie et Génomique Structurales, Institut de Génétique et de Biologie Moléculaire et Cellulaire, (CNRS/INSERM/ULP), Illkirch Cedex, 67404, France.

Journal of Molecular Biology
|December 6, 2001
PubMed
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We developed norMD, a new objective scoring function for multiple sequence alignments. This method improves accuracy in functional and evolutionary studies by incorporating sequence characteristics and similarity, enhancing genome annotation.

Area of Science:

  • Bioinformatics
  • Computational Biology
  • Genomics

Background:

  • Multiple sequence alignment is crucial for functional and evolutionary studies in molecular biology.
  • Integrated genome annotation systems rely heavily on multiple alignments.
  • There is a need for improved scoring functions for multiple sequence alignments.

Purpose of the Study:

  • To introduce norMD, a novel objective scoring function for multiple sequence alignments.
  • To enhance the accuracy and reliability of multiple sequence alignment scoring.
  • To improve the process of genome annotation and analysis.

Main Methods:

  • Developed norMD, combining column-scoring and residue similarity.
  • Incorporated ab initio sequence information (number, length, similarity).

Related Experiment Videos

  • Validated norMD using structural alignments from SCOP and BAliBASE databases.

    • Main Results:

    • norMD demonstrated sensitivity and reliability in structural alignment validation.
    • Applied norMD to multiple alignments of Vibrio cholerae hypothetical proteins.
    • Automatically removed unreliable sequences, resulting in high-quality multiple alignments.

    Conclusions:

    • norMD facilitates reliable functional and structural annotation.
    • 24% of alignments revealed new functional annotations after norMD application.
    • 103 new matches were supported by InterPro domain and motif database hits.