All Publications

  • Genome-wide profiling of 24 hr diel rhythmicity in the water flea, Daphnia pulex: network analysis reveals rhythmic gene expression and enhances functional gene annotation BMC GENOMICS Rund, S. S., Yoo, B., Alam, C., Green, T., Stephens, M. T., Zeng, E., George, G. F., Sheppard, A. D., Duffield, G. E., Milenkovic, T., Pfrender, M. E. 2016; 17


    Marine and freshwater zooplankton exhibit daily rhythmic patterns of behavior and physiology which may be regulated directly by the light:dark (LD) cycle and/or a molecular circadian clock. One of the best-studied zooplankton taxa, the freshwater crustacean Daphnia, has a 24 h diel vertical migration (DVM) behavior whereby the organism travels up and down through the water column daily. DVM plays a critical role in resource tracking and the behavioral avoidance of predators and damaging ultraviolet radiation. However, there is little information at the transcriptional level linking the expression patterns of genes to the rhythmic physiology/behavior of Daphnia.Here we analyzed genome-wide temporal transcriptional patterns from Daphnia pulex collected over a 44 h time period under a 12:12 LD cycle (diel) conditions using a cosine-fitting algorithm. We used a comprehensive network modeling and analysis approach to identify novel co-regulated rhythmic genes that have similar network topological properties and functional annotations as rhythmic genes identified by the cosine-fitting analyses. Furthermore, we used the network approach to predict with high accuracy novel gene-function associations, thus enhancing current functional annotations available for genes in this ecologically relevant model species. Our results reveal that genes in many functional groupings exhibit 24 h rhythms in their expression patterns under diel conditions. We highlight the rhythmic expression of immunity, oxidative detoxification, and sensory process genes. We discuss differences in the chronobiology of D. pulex from other well-characterized terrestrial arthropods.This research adds to a growing body of literature suggesting the genetic mechanisms governing rhythmicity in crustaceans may be divergent from other arthropod lineages including insects. Lastly, these results highlight the power of using a network analysis approach to identify differential gene expression and provide novel functional annotation.

    View details for DOI 10.1186/s12864-016-2998-2

    View details for Web of Science ID 000384053500003

    View details for PubMedID 27538446

    View details for PubMedCentralID PMC4991082

  • Improving identification of key players in aging via network de-noising and core inference. IEEE/ACM transactions on computational biology and bioinformatics / IEEE, ACM Yoo, B. n., Faisal, F. n., Chen, H. n., Milenkovic, T. n. 2015


    Current "ground truth" knowledge about human aging has been obtained by transferring aging-related knowledge from well-studied model species via sequence homology or by studying human gene expression data. Since proteins function by interacting with each other, analyzing protein-protein interaction (PPI) networks in the context of aging is promising. Unlike existing static network research of aging, since cellular functioning is dynamic, we recently integrated the static human PPI network with aging-related gene expression data to form dynamic, age-specific networks. Then, we predicted as key players in aging those proteins whose network topologies significantly changed with age. Since current networks are noisy, here, we use link prediction to de-noise the human network and predict improved key players in aging from the de-noised data. Indeed, de-noising gives more significant overlap between the predicted data and the "ground truth" aging-related data. Yet, we obtain novel predictions, which we validate in the literature. Also, we improve the predictions by an alternative strategy: removing "redundant" edges from the age-specific networks and using the resulting age-specific network "cores" to study aging. We produce new knowledge from dynamic networks encompassing multiple data types, via network de-noising or core inference, complementing the existing knowledge obtained from sequence or expression data.

    View details for DOI 10.1109/TCBB.2015.2495170

    View details for PubMedID 26529776