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. 2008 Sep;15(7):655-65.
doi: 10.1089/cmb.2007.0114.

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

Anthony A Philippakis  1 , Aaron M Qureshi, Michael F Berger, Martha L Bulyk
Affiliations

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

Anthony A Philippakis et al. J Comput Biol. 2008 Sep.

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). 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 pseudo-randomness 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.

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Figures

FIG. 1.
FIG. 1.
De Bruijn sequence of order 2 (a) and its associated de Bruijn graph (b).
FIG. 2.
FIG. 2.
Addition and multiplication tables over GF(4).
FIG. 3.
FIG. 3.
Generation of de Bruijn sequences over 4-letter (a) and 2-letter (b) alphabets.
FIG. 4.
FIG. 4.
Cartoon depicting all m-mers (gray vertices) and m-mers samples by an order k < m de Bruijn sequence (black vertices). Vertices are connected by an edge if they are 1 mismatch away. (a) de Bruijn sequence that samples m-mers randomly. (b) de Bruijn sequence that samples m-mers regularly.
See this image and copyright information in PMC

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