Publications

Early pathogen exposure detection allows better patient care and faster implementation of public health measures (patient isolation, contact tracing). Existing exposure detection most frequently relies on overt clinical symptoms, namely fever, during the infectious prodromal period. We have developed a robust machine learning based method to better detect asymptomatic states during the incubation period using subtle, sub-clinical physiological markers. Starting with highresolution physiological waveform data from non-human primate studies of viral (Ebola, Marburg, Lassa, and Nipah viruses) and bacterial (Y. pestis) exposure, we processed the data to reduce short-term variability and normalize diurnal variations, then provided these to a supervised random forest classification algorithm and post-classifier declaration logic step to reduce false alarms. In most subjects detection is achieved well before the onset of fever; subject cross-validation across exposure studies (varying viruses, exposure routes, animal species, and target dose) lead to 51h mean early detection (at 0.93 area under the receiver-operating characteristic curve [AUCROC]). Evaluating the algorithm against entirely independent datasets for Lassa, Nipah, and Y. pestis exposures un-used in algorithm training and development yields a mean 51h early warning time (at AUCROC=0.95). We discuss which physiological indicators are most informative for early detection and options for extending this capability to limited datasets such as those available from wearable, non-invasive, ECG-based sensors.

With advances in high throughput brain imaging at the cellular and sub-cellular level, there is growing demand for platforms that can support high performance, large-scale brain data processing and analysis. In this paper, we present a novel pipeline that combines Accumulo, D4M, geohashing, and parallel programming to manage large-scale neuron connectivity graphs in a cloud environment. Our brain connectivity graph is represented using vertices (fiber start/end nodes), edges (fiber tracks), and the 3D coordinates of the fiber tracks. For optimal performance, we take the hybrid approach of storing vertices and edges in Accumulo and saving the fiber track 3D coordinates in flat files. Accumulo database operations offer low latency on sparse queries while flat files offer high throughput for storing, querying, and analyzing bulk data. We evaluated our pipeline by using 250 gigabytes of mouse neuron connectivity data. Benchmarking experiments on retrieving vertices and edges from Accumulo demonstrate that we can achieve 1-2 orders of magnitude speedup in retrieval time when compared to the same operation from traditional flat files. The implementation of graph analytics such as Breadth First Search using Accumulo and D4M offers consistent good performance regardless of data size and density, thus is scalable to very large dataset. Indexing of neuron subvolumes is simple and logical with geohashing-based binary tree encoding. This hybrid data management backend is used to drive an interactive web-based 3D graphical user interface, where users can examine the 3D connectivity map in a Google Map-like viewer. Our pipeline is scalable and extensible to other data modalities.

Early pathogen exposure detection allows better patient care and faster implementation of public health measures (patient isolation, contact tracing). Existing exposure detection most frequently relies on overt clinical symptoms, namely fever, during the infectious prodromal period. We have developed a robust machine learning method to better detect asymptomatic states during the incubation period using subtle, sub-clinical physiological markers. Using high-resolution physiological data from non-human primate studies of Ebola and Marburg viruses, we pre-processed the data to reduce short-term variability and normalize diurnal variations, then provided these to a supervised random forest classification algorithm. In most subjects detection is achieved well before the onset of fever; subject cross-validation lead to 52±14h mean early detection (at >0.90 area under the receiver-operating characteristic curve). Cross-cohort tests across pathogens and exposure routes also lead to successful early detection (28±16h and 43±22h, respectively). We discuss which physiological indicators are most informative for early detection and options for extending this capability to lower data resolution and wearable, non-invasive sensors.