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Prediction pipeline for discovery of regulatory motifs associated with Brugia malayi molting
- Source :
- PLoS Neglected Tropical Diseases, PLoS Neglected Tropical Diseases, Vol 14, Iss 6, p e0008275 (2020)
- Publication Year :
- 2020
- Publisher :
- Public Library of Science, 2020.
-
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 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.<br />Author summary Diseases caused by parasitic worms such as the filariae are among the leading causes of morbidity in the developing world. Very little is known about how development is regulated in these vector-transmitted parasites. We have developed a computational method to identify motifs that correspond to transcription factor binding sites in the genome of the parasitic worm, Brugia malayi, one of the causative agents of lymphatic filariasis. Using this approach, we were able to predict stage-specific transcription factor binding sites involved in a stage of the molting process important for the establishment of the infection. We validated the role of these motifs using an in vitro molting system.
- Subjects :
- 0301 basic medicine
Life Cycles
Nematoda
Physiology
RC955-962
Gene Expression
Helminth genetics
Molting
Genome
Biochemistry
Brugia malayi
Database and Informatics Methods
0302 clinical medicine
Larvae
Arctic medicine. Tropical medicine
Medicine and Health Sciences
Brugia Malayi
Caenorhabditis elegans
Genes, Helminth
Oligonucleotide Array Sequence Analysis
biology
Eukaryota
Animal Models
Infectious Diseases
Experimental Organism Systems
Larva
Public aspects of medicine
RA1-1270
Sequence Analysis
Research Article
Bioinformatics
030231 tropical medicine
Computational biology
Research and Analysis Methods
03 medical and health sciences
Model Organisms
Sequence Motif Analysis
parasitic diseases
DNA-binding proteins
Brugia
Genetics
Animals
Gene Regulation
Gene
Transcription factor
Base Sequence
Gene Expression Profiling
Public Health, Environmental and Occupational Health
Organisms
Biology and Life Sciences
Proteins
biology.organism_classification
Onchocerca volvulus
Invertebrates
Regulatory Proteins
Gene expression profiling
030104 developmental biology
Animal Studies
Caenorhabditis
RNA, Helminth
Physiological Processes
Developmental Biology
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 19352735 and 19352727
- Volume :
- 14
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- PLoS Neglected Tropical Diseases
- Accession number :
- edsair.doi.dedup.....8fdea8b77a7fcaa689f5ed0fd0151825