Professional Education

  • Doctor of Philosophy, Boston University (2019)
  • Bachelors of Science, Alexandru Ioan Cuza University of Iasi (2012)

Stanford Advisors

All Publications

  • Inferring microbial co-occurrence networks from amplicon data: a systematic evaluation. mSystems Kishore, D., Birzu, G., Hu, Z., DeLisi, C., Korolev, K. S., Segrè, D. 2023: e0096122


    Microbes commonly organize into communities consisting of hundreds of species involved in complex interactions with each other. 16S ribosomal RNA (16S rRNA) amplicon profiling provides snapshots that reveal the phylogenies and abundance profiles of these microbial communities. These snapshots, when collected from multiple samples, can reveal the co-occurrence of microbes, providing a glimpse into the network of associations in these communities. However, the inference of networks from 16S data involves numerous steps, each requiring specific tools and parameter choices. Moreover, the extent to which these steps affect the final network is still unclear. In this study, we perform a meticulous analysis of each step of a pipeline that can convert 16S sequencing data into a network of microbial associations. Through this process, we map how different choices of algorithms and parameters affect the co-occurrence network and identify the steps that contribute substantially to the variance. We further determine the tools and parameters that generate robust co-occurrence networks and develop consensus network algorithms based on benchmarks with mock and synthetic data sets. The Microbial Co-occurrence Network Explorer, or MiCoNE (available at follows these default tools and parameters and can help explore the outcome of these combinations of choices on the inferred networks. We envisage that this pipeline could be used for integrating multiple data sets and generating comparative analyses and consensus networks that can guide our understanding of microbial community assembly in different biomes. IMPORTANCE Mapping the interrelationships between different species in a microbial community is important for understanding and controlling their structure and function. The surge in the high-throughput sequencing of microbial communities has led to the creation of thousands of data sets containing information about microbial abundances. These abundances can be transformed into co-occurrence networks, providing a glimpse into the associations within microbiomes. However, processing these data sets to obtain co-occurrence information relies on several complex steps, each of which involves numerous choices of tools and corresponding parameters. These multiple options pose questions about the robustness and uniqueness of the inferred networks. In this study, we address this workflow and provide a systematic analysis of how these choices of tools affect the final network and guidelines on appropriate tool selection for a particular data set. We also develop a consensus network algorithm that helps generate more robust co-occurrence networks based on benchmark synthetic data sets.

    View details for DOI 10.1128/msystems.00961-22

    View details for PubMedID 37338270

  • Hybridization breaks species barriers in long-term coevolution of a cyanobacterial population. bioRxiv : the preprint server for biology Birzu, G., Muralidharan, H. S., Goudeau, D., Malmstrom, R. R., Fisher, D. S., Bhaya, D. 2023


    Bacterial species often undergo rampant recombination yet maintain cohesive genomic identity. Ecological differences can generate recombination barriers between species and sustain genomic clusters in the short term. But can these forces prevent genomic mixing during long-term coevolution? Cyanobacteria in Yellowstone hot springs comprise several diverse species that have coevolved for hundreds of thousands of years, providing a rare natural experiment. By analyzing more than 300 single-cell genomes, we show that despite each species forming a distinct genomic cluster, much of the diversity within species is the result of hybridization driven by selection, which has mixed their ancestral genotypes. This widespread mixing is contrary to the prevailing view that ecological barriers can maintain cohesive bacterial species and highlights the importance of hybridization as a source of genomic diversity.

    View details for DOI 10.1101/2023.06.06.543983

    View details for PubMedID 37333348

    View details for PubMedCentralID PMC10274767

  • Genealogical structure changes as range expansions transition from pushed to pulled. Proceedings of the National Academy of Sciences of the United States of America Birzu, G., Hallatschek, O., Korolev, K. S. 2021; 118 (34)


    Range expansions accelerate evolution through multiple mechanisms, including gene surfing and genetic drift. The inference and control of these evolutionary processes ultimately rely on the information contained in genealogical trees. Currently, there are two opposing views on how range expansions shape genealogies. In invasion biology, expansions are typically approximated by a series of population bottlenecks producing genealogies with only pairwise mergers between lineages-a process known as the Kingman coalescent. Conversely, traveling wave models predict a coalescent with multiple mergers, known as the Bolthausen-Sznitman coalescent. Here, we unify these two approaches and show that expansions can generate an entire spectrum of coalescent topologies. Specifically, we show that tree topology is controlled by growth dynamics at the front and exhibits large differences between pulled and pushed expansions. These differences are explained by the fluctuations in the total number of descendants left by the early founders. High growth cooperativity leads to a narrow distribution of reproductive values and the Kingman coalescent. Conversely, low growth cooperativity results in a broad distribution, whose exponent controls the merger sizes in the genealogies. These broad distribution and non-Kingman tree topologies emerge due to the fluctuations in the front shape and position and do not occur in quasi-deterministic simulations. Overall, our results show that range expansions provide a robust mechanism for generating different types of multiple mergers, which could be similar to those observed in populations with strong selection or high fecundity. Thus, caution should be exercised in making inferences about the origin of non-Kingman genealogies.

    View details for DOI 10.1073/pnas.2026746118

    View details for PubMedID 34413189