Causal Inference in Disease Spread across a Heterogeneous Social System

Diffusion processes are governed by external triggers and internal dynamics in complex systems. Timely and cost-effective control of infectious disease spread critically relies on uncovering the underlying diffusion mechanisms, which is challenging due to invisible causality between events and their time-evolving intensity. We infer causal relationships between infections and quantify the reflexivity of a meta-population, the level of feedback on event occurrences by its internal dynamics (likelihood of a regional outbreak triggered by previous cases). These are enabled by our new proposed model, the Latent Influence Point Process (LIPP) which models disease spread by incorporating macro-level internal dynamics of meta-populations based on human mobility. We analyse 15-year dengue cases in Queensland, Australia. From our causal inference, outbreaks are more likely driven by statewide global diffusion over time, leading to complex behavior of disease spread. In terms of reflexivity, precursory growth and symmetric decline in populous regions is attributed to slow but persistent feedback on preceding outbreaks via inter-group dynamics, while abrupt growth but sharp decline in peripheral areas is led by rapid but inconstant feedback via intra-group dynamics. Our proposed model reveals probabilistic causal relationships between discrete events based on intra- and inter-group dynamics and also covers direct and indirect diffusion processes (contact-based and vector-borne disease transmissions).Comment: arXiv admin note: substantial text overlap with arXiv:1711.0635

Complementary Metagenomic Approaches Improve Reconstruction of Microbial Diversity in a Forest Soil.

Soil ecosystems harbor diverse microorganisms and yet remain only partially characterized as neither single-cell sequencing nor whole-community sequencing offers a complete picture of these complex communities. Thus, the genetic and metabolic potential of this "uncultivated majority" remains underexplored. To address these challenges, we applied a pooled-cell-sorting-based mini-metagenomics approach and compared the results to bulk metagenomics. Informatic binning of these data produced 200 mini-metagenome assembled genomes (sorted-MAGs) and 29 bulk metagenome assembled genomes (MAGs). The sorted and bulk MAGs increased the known phylogenetic diversity of soil taxa by 7.2% with respect to the Joint Genome Institute IMG/M database and showed clade-specific sequence recruitment patterns across diverse terrestrial soil metagenomes. Additionally, sorted-MAGs expanded the rare biosphere not captured through MAGs from bulk sequences, exemplified through phylogenetic and functional analyses of members of the phylum Bacteroidetes Analysis of 67 Bacteroidetes sorted-MAGs showed conserved patterns of carbon metabolism across four clades. These results indicate that mini-metagenomics enables genome-resolved investigation of predicted metabolism and demonstrates the utility of combining metagenomics methods to tap into the diversity of heterogeneous microbial assemblages.IMPORTANCE Microbial ecologists have historically used cultivation-based approaches as well as amplicon sequencing and shotgun metagenomics to characterize microbial diversity in soil. However, challenges persist in the study of microbial diversity, including the recalcitrance of the majority of microorganisms to laboratory cultivation and limited sequence assembly from highly complex samples. The uncultivated majority thus remains a reservoir of untapped genetic diversity. To address some of the challenges associated with bulk metagenomics as well as low throughput of single-cell genomics, we applied flow cytometry-enabled mini-metagenomics to capture expanded microbial diversity from forest soil and compare it to soil bulk metagenomics. Our resulting data from this pooled-cell sorting approach combined with bulk metagenomics revealed increased phylogenetic diversity through novel soil taxa and rare biosphere members. In-depth analysis of genomes within the highly represented Bacteroidetes phylum provided insights into conserved and clade-specific patterns of carbon metabolism