Genetic interactions underlie mechanisms of all heredity diseases. By revealing how one gene activity affects the function of another, genetic interaction studies complement other genomic approaches such as protein-protein interaction studies by providing direct evidence of functional relations among genes, offering answers to questions such as functional redundancy and genetic epistasis that other approaches can not resolve. Genetic interaction research becomes especially important when studying disease genes, because human genetic diseases often result from a combined action of multiple genes. My long-term research goal is to reach a system level understanding of the genetic interaction network. I am interested in combining my expertise in experimental biology and computer science to design high-throughput tools and apply these tools to study genetic interactions at genome scale. The objective of this application is to generate a large-scale, quantitative genetic interaction map of disease genes in the metazoan model C. elegans. To accomplish this, I have developed a high-throughput pipeline for predicting and testing of genetic interactions in C. elegans. The first component of the pipeline is a computational system that generates genome-wide probabilistic predictions of genetic interactions by integrating expression, phenotype, interaction, and function data from multiple species. The second component of the pipeline is a high-speed automatic phenotyping system that uses automatic microscopy and image processing to provide quantitative measurements of nematode phenotypes. I plan to apply the established tools to systematically investigate the interactions of human disease gene homologs in C. elegans. A multi-phenotypic, quantitative model of the disease gene interaction network will be generated. For each disease gene, I wili identify its interacting partners, the type of interaction between each gene pair, and the biological process for each interaction.

Public Health Relevance

This study is relevant to public health because it brings insights to disease mechanisms and it provides an efficient system to identify new targets for preventive and therapeutic intervention of human heredity diseases.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Transition Award (R00)
Project #
5R00HG004724-04
Application #
8119149
Study Section
Special Emphasis Panel (NSS)
Program Officer
Feingold, Elise A
Project Start
2008-09-10
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2013-06-30
Support Year
4
Fiscal Year
2011
Total Cost
$249,000
Indirect Cost
Name
Rice University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
050299031
City
Houston
State
TX
Country
United States
Zip Code
77005
Aleman-Meza, Boanerges; Loeza-Cabrera, Mario; Peña-Ramos, Omar et al. (2017) High-content behavioral profiling reveals neuronal genetic network modulating Drosophila larval locomotor program. BMC Genet 18:40
Zhou, Ying; Loeza-Cabrera, Mario; Liu, Zheng et al. (2017) Potential Nematode Alarm Pheromone Induces Acute Avoidance in Caenorhabditis elegans. Genetics 206:1469-1478
Labocha, Marta K; Yuan, Wang; Aleman-Meza, Boanerges et al. (2017) A strategy to apply quantitative epistasis analysis on developmental traits. BMC Genet 18:42
Jung, Sang-Kyu; Qu, Xiaolei; Aleman-Meza, Boanerges et al. (2015) Multi-endpoint, high-throughput study of nanomaterial toxicity in Caenorhabditis elegans. Environ Sci Technol 49:2477-85
Aleman-Meza, Boanerges; Jung, Sang-Kyu; Zhong, Weiwei (2015) An automated system for quantitative analysis of Drosophila larval locomotion. BMC Dev Biol 15:11
Labocha, Marta K; Jung, Sang-Kyu; Aleman-Meza, Boanerges et al. (2015) WormGender - Open-Source Software for Automatic Caenorhabditis elegans Sex Ratio Measurement. PLoS One 10:e0139724
Contreras, Elizabeth Q; Puppala, Hema L; Escalera, Gabriela et al. (2014) Size-dependent impacts of silver nanoparticles on the lifespan, fertility, growth, and locomotion of Caenorhabditis elegans. Environ Toxicol Chem 33:2716-23
Jung, Sang-Kyu; Aleman-Meza, Boanerges; Riepe, Celeste et al. (2014) QuantWorm: a comprehensive software package for Caenorhabditis elegans phenotypic assays. PLoS One 9:e84830
Guo, Yusong R; Hryc, Corey F; Jakana, Joanita et al. (2014) Crystal structure of a nematode-infecting virus. Proc Natl Acad Sci U S A 111:12781-6
Contreras, Elizabeth Q; Cho, Minjung; Zhu, Huiguang et al. (2013) Toxicity of quantum dots and cadmium salt to Caenorhabditis elegans after multigenerational exposure. Environ Sci Technol 47:1148-54

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