TY - JOUR
T1 - Prediction pipeline for discovery of regulatory motifs associated with brugia Malayi molting
AU - Grote, Alexandra
AU - Li, Yichao
AU - Liu, Canhui
AU - Voronin, Denis
AU - Geber, Adam
AU - Lustigman, Sara
AU - Unnasch, Thomas R.
AU - Welch, Lonnie
AU - Ghedin, Elodie
N1 - Publisher Copyright:
© 2020 Grote et al.
PY - 2020/6
Y1 - 2020/6
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pntd.0008275
DO - 10.1371/journal.pntd.0008275
M3 - Article
C2 - 32574217
AN - SCOPUS:85087371430
SN - 1935-2727
VL - 14
SP - 1
EP - 16
JO - PLoS neglected tropical diseases
JF - PLoS neglected tropical diseases
IS - 6
M1 - e0008275
ER -