Design of compact, universal DNA microarrays for protein binding microarray experiments

  • Authors:

  • Anthony A. Philippakis;Aaron M. Qureshi;Michael F. Berger;Martha L. Bulyk

  • Affiliations:

  • Division of Genetics, Department of Medicine and Harvard, MIT Division of Health Sciences and Technology, Cambridge, MA and Harvard University Graduate Biophysics Program, Cambridge, MA;Division of Genetics, Department of Medicine and Department of Mathematics, University of Maryland, College Park, MD;Division of Genetics, Department of Medicine and Harvard University Graduate Biophysics Program, Cambridge, MA;Div. of Genetics, Dept. of Med. and Dept. of Pathology, Brigham and Women's Hospital and Harvard Med. School, Boston, MA and Harvard, MIT Div. of Health Sci. and Techn., Cambridge, MA and Harvard ...

  • Venue:
  • RECOMB'07 Proceedings of the 11th annual international conference on Research in computational molecular biology
  • Year:
  • 2007

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Abstract

Our group has recently developed a compact, universal protein binding microarray (PBM) that can be used to determine the binding preferences of transcription factors (TFs) [1]. This design represents all possible sequence variants of a given length k (i.e., all k-mers) on a single array, allowing a complete characterization of the binding specificities of a given TF. Here, we present the mathematical foundations of this design based on de Bruijn sequences generated by linear feedback shift registers. We show that these sequences represent the maximum number of variants for any given set of array dimensions (i.e., number of spots and spot lengths), while also exhibiting desirable pseudorandomness properties. Moreover, de Bruijn sequences can be selected that represent gapped sequence patterns, further increasing the coverage of the array. This design yields a powerful experimental platform that allows the binding preferences of TFs to be determined with unprecedented resolution.