Prediction pipeline for discovery of regulatory motifs associated with Brugia malayi molting.


Journal

PLoS neglected tropical diseases
ISSN: 1935-2735
Titre abrégé: PLoS Negl Trop Dis
Pays: United States
ID NLM: 101291488

Informations de publication

Date de publication:
06 2020
Historique:
received: 14 11 2019
accepted: 07 04 2020
revised: 06 07 2020
pubmed: 24 6 2020
medline: 11 8 2020
entrez: 24 6 2020
Statut: epublish

Résumé

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 available, 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-living 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 system, we tested and validated three of these motifs demonstrating the accuracy of the motif prediction pipeline.

Identifiants

pubmed: 32574217
doi: 10.1371/journal.pntd.0008275
pii: PNTD-D-19-01897
pmc: PMC7337397
doi:

Substances chimiques

RNA, Helminth 0
Transcription Factors 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0008275

Subventions

Organisme : NIAID NIH HHS
ID : R56 AI101372
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI126466
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007180
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI135172
Pays : United States
Organisme : NIAID NIH HHS
ID : F31 AI131527
Pays : United States

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Alexandra Grote (A)

Department of Biology, Center for Genomics and Systems Biology, New York University, New York, New York, United States of America.

Yichao Li (Y)

School of Computer Science and Electrical Engineering, Ohio University, Athens, Ohio, United States of America.

Canhui Liu (C)

Center for Global Infectious Disease Research, University of South Florida, Tampa, FL, Florida, United States of America.

Denis Voronin (D)

Laboratory of Molecular Parasitology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, United States of America.

Adam Geber (A)

Department of Biology, Center for Genomics and Systems Biology, New York University, New York, New York, United States of America.

Sara Lustigman (S)

Laboratory of Molecular Parasitology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, United States of America.

Thomas R Unnasch (TR)

Center for Global Infectious Disease Research, University of South Florida, Tampa, FL, Florida, United States of America.

Lonnie Welch (L)

School of Computer Science and Electrical Engineering, Ohio University, Athens, Ohio, United States of America.

Elodie Ghedin (E)

Department of Biology, Center for Genomics and Systems Biology, New York University, New York, New York, United States of America.
Department of Epidemiology, School of Global Public Health, New York University, New York, New York, United States of America.

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Classifications MeSH