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Lawrence S Hon

Publications and source records attributed to Lawrence S Hon.

2 recordsLinked to original sources

A deterministic motif finding algorithm with application to the human genome.

MOTIVATION: We present a novel algorithm, MaMF, for identifying transcription factor (TF) binding site motifs. The method is deterministic and depends on an indexing technique to optimize the search process. On common yeast datasets, MaMF performs competitively with other methods. We also present results on a challenging group of eight sets of human genes known to be responsive to a diverse group of TFs. In every case, MaMF finds the annotated motif among the top scoring putative motifs. We compared MaMF against other motif finders on a larger human group of 21 gene sets and found that MaMF performs better than other algorithms. We analyzed the remaining high scoring motifs and show that many correspond to other TFs that are known to co-occur with the annotated TF motifs. The significant and frequent presence of co-occurring transcription factor binding sites explains in part the difficulty of human motif finding. MaMF is a very fast algorithm, suitable for application to large numbers of interesting gene sets.

Algorithms↗

Compositional structure of repetitive elements is quantitatively related to co-expression of gene pairs.

A sequence similarity metric operating on 10 kb upstream regions of gene pairs quantitatively predicts a portion of co-variation of expression of gene pairs in large-scale gene expression studies in human tumors and tumor-derived cell lines. The signal on which the metric depends most strongly originates in the compositional structure of repetitive genomic sequences (particularly Alu elements) present in these upstream regions. This effect is completely separable from effects of isochore composition on gene expression. The results implicate repetitive elements with some functional role in transcriptional regulation of the specific genes in whose promoter regions they reside and lend credence to suggestions that the general phenomenon of repetitive element insertions may be a fundamental evolutionary mechanism for modulating gene transcription.

Base Composition↗