Prediction pipeline for discovery of regulatory motifs associated with brugia Malayi molting

Alexandra Grote, Yichao Li, Canhui Liu, Denis Voronin, Adam Geber, Sara Lustigman, Thomas R. Unnasch, Lonnie Welch, Elodie Ghedin

Research output: Contribution to journalArticlepeer-review

Abstract

Filarial nematodes can cause debilitating diseases in humans. They have complicated life cycles involving an insect vector and mammalian hosts, and they go through a number of developmental molts. While whole genome sequences of parasitic worms are now avail-able, very little is known about transcription factor (TF) binding sites and their cognate transcription factors that play a role in regulating development. To address this gap, we developed a novel motif prediction pipeline, Emotif Alpha, that integrates ten different motif discovery algorithms, multiple statistical tests, and a comparative analysis of conserved elements between the filarial worms Brugia malayi and Onchocerca volvulus, and the free-liv-ing nematode Caenorhabditis elegans. We identified stage-specific TF binding motifs in B. malayi, with a particular focus on those potentially involved in the L3-L4 molt, a stage important for the establishment of infection in the mammalian host. Using an in vitro molting sys-tem, we tested and validated three of these motifs demonstrating the accuracy of the motif prediction pipeline.

Original languageEnglish (US)
Article numbere0008275
Pages (from-to)1-16
Number of pages16
JournalPLoS neglected tropical diseases
Volume14
Issue number6
DOIs
StatePublished - Jun 2020

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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