Biological organisms form a complex network of interacting elements: genes, mRNA transcripts, proteins, metabolites, cells. These organisms are then embedded in networks of interactions: social networks among interacting members of a population, and ecological networks of interactions between species (host-parasite, host-microbe, microbe-microbe). As the populations in our study adapt to their new lakes, we expect to see changes in all of these networks. This poses a significant statistical challenge, because the science of complex networks has long been focused on how to measure network properties. Far less attention has been devoted to the question of how to measure changes in networks (and confirm these are statistically convincing). This team is a partnership between evolutionary biologists, network scientists, computer scientists, and statisticians. We seek to gather biological data about networks (gene expression networks, metabolomic networks, microbial networks, and ecological networks), and quantify how network properties evolve and change across generations. Concurrently, we are working to develop new approaches to statistically analyzing biological networks, testing hypotheses about network change, and interpreting these changes' biological meaning. This interdisciplinary collaboration is supported by a U.S. National Science Foundation “Rules of Life: Emerging Networks” grant.
Transcriptomics involves studying all RNA molecules in a cell to understand which proteins are being transcribed from DNA. Together with Prof. Daniel Bolnick, Dr. Rogini Runghen is working on evaluating changes in gene expression networks through time and divergence in populations over time. To do this, we collect samples from all source and recipient lakes each year to analyse transcriptomic data from head kidneys and liver tissues. Network changes over time and between populations will underlie shifts in higher-order phenotypes. This work is done in collaboration with Prof. Jesse Weber and Emily Kerns, we are also evaluating plasticity and heritability of co-expression network differences.
Interpreting transcriptomic data from bulk tissue (a mix of cell types) is complicated, because gene expression is confounded with changes in different cell types’ abundance. Dr. Tina Eliassi-Rad, Wan He and Dr. Sam Scarpino are developing new methods for drawing inferences about cell clusters from scRNAseq data. When applied to stickleback scRNAseq data, this will give us cell-type gene expression profiles that help us interpret the bulk transcriptomic data.
We partnered with the Gordon and Betty Moore Foundation to generate metabolomic data from stickleback in 2023. In collaboration with Dr. Marwa Tawfiq, we are using Liquid Chromatography Mass-Spec (LC-MS-MS) to quantify liver metabolomics of stickleback from each experimental lake. The data will be related to diet, parasite status, gene expression, and microbiota using a multi-layer network analysis approach. We are interested in knowing how these networks differ between phenotypes (sex, size, infection status, etc) and between populations.
Led by Dr. Kathryn Milligan-McClellan, we are sequencing gut microbiota of approximately 50 fish per lake each year. We will quantify host-microbe (bipartite) and microbe-microbe networks and how these network properties are changing during the course of population adaptation.
Led by Dr. Miaoyan Wang and Jiaxin Hu, we have developed new methods for doing gene expression Quantitative Trait Locus (QTL) mapping to find genes that are polymorphic and alter the overall structure of the gene co-expression network. These high-leverage loci within the network require statistical comparisons between multiple networks.
We are using network analysis methods to quantify changes in dietary networks through time and between populations. At present this work has been led by PhD student Pamela Friedemann (University Sao Paulo, Brazil), who used gut content analysis to quantify stickleback-prey networks in the recipient lakes and show that network structures have diverged.
Merging all of the above, we hope to evaluate how changes in gene expression networks, metabolomic networks, microbiota networks, and diet and infection networks, collectively are inter-related. This will use multi-level network analysis to identify connections between the different types of biological networks.
Principal Investigator
Northeastern University, USA
2022 - present
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Collaborator
Aberdeen University, Scotland
2023 - present
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PhD candidate
University of Wisconsin-Madison, USA
2022 - present
PhD student
Northeastern University, USA
2022 - present
PhD student
University of São Paolo, Brazil
2022 - present
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