Scholarship & Research
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Item Leveraging social networks for identification of people living with HIV who are virally unsuppressed(Wolters Kluwer Health, Inc., 2023-10) Cummins, Breschine; Johnson, Kara; Schneider, John A.; Del Vicchio, Natasha; Moshiri, Niema; Wertheim, Joel O.; Goyal, Ravi; Skaathun, BrittObjectives: This study investigates primary peer-referral engagement (PRE) strategies to assess which strategy results in engaging higher numbers of people living with HIV (PLWH) who are virally unsuppressed. Design: We develop a modeling study that simulates an HIV epidemic (transmission, disease progression, and viral evolution) over 6 years using an agent-based model followed by simulating PRE strategies. We investigate two PRE strategies where referrals are based on social network strategies (SNS) or sexual partner contact tracing (SPCT). Methods: We parameterize, calibrate, and validate our study using data from Chicago on Black sexual minority men to assess these strategies for a population with high incidence and prevalence of HIV. For each strategy we calculate the number of PLWH recruited who are undiagnosed or out-of-care and the number of direct or indirect transmissions. Results: SNS and SPCT identified 256.5 (95% C.I.: [234,279]) and 15 (95% C.I.: [7,27]) PLWH, respectively. Of these, SNS identified 159 (95% C.I.: [142,177]) PLWH out-of-care and 32 (95% C.I.: [21, 43]]) PLWH undiagnosed compared to 9 (95% C.I.: [3,18]) and 2 (95% C.I.: [0,5]) for SPCT. SNS identified 15.5 (95% C.I.: [6,25]) and 7.5 (95% C.I.: [2, 11]]) indirect and direct transmission pairs, while SPCT identified 6 (95% C.I.: [0,8]) and 5 (95% C.I.: [0,8]), respectively. Conclusions: With no testing constraints, SNS is the more effective strategy to identify undiagnosed and out-of-care PLWH. Neither strategy is successful at identifying sufficient indirect or direct transmission pairs to investigate transmission networks.Item Experimental guidance for discovering genetic networks through hypothesis reduction on time series(Public Library of Science, 2022-10) Cummins, Breschine; Motta, Francis C.; Moseley, Robert C.; Deckard, Anastasia; Campione, Sophia; Gedeon, Tomáš; Mischaikow, Konstantin; Haase, Steven B.Large programs of dynamic gene expression, like cell cyles and circadian rhythms, are controlled by a relatively small “core” network of transcription factors and post-translational modifiers, working in concerted mutual regulation. Recent work suggests that system-independent, quantitative features of the dynamics of gene expression can be used to identify core regulators. We introduce an approach of iterative network hypothesis reduction from time-series data in which increasingly complex features of the dynamic expression of individual, pairs, and entire collections of genes are used to infer functional network models that can produce the observed transcriptional program. The culmination of our work is a computational pipeline, Iterative Network Hypothesis Reduction from Temporal Dynamics (Inherent dynamics pipeline), that provides a priority listing of targets for genetic perturbation to experimentally infer network structure. We demonstrate the capability of this integrated computational pipeline on synthetic and yeast cell-cycle data.Item Highly-automated, high-throughput replication of yeast-based logic circuit design assessments(Oxford University Press, 2022-02) Goldman, Robert P; Moseley, Robert; Roehner, Nicholas; Cummins, Breschine; Vrana, Justin D; Clowers, Katie J; Bryce, Daniel; Beal, Jacob; DeHaven, Matthew; Nowak, Joshua; Higa, Trissha; Biggers, Vanessa; Lee, Peter; Hunt, Jeremy P.; Mosqueda, Lorraine; Haase, Steven B.; Weston, Mark; Zheng, George; Deckard, Anastasia; Gopaulakrishnan, Shweta; Stubbs, Joseph F.; Gaffney, Niall I.; Vaughn, Matthew W.; Maheshri, Narendra; Mikhalev, Ekaterina; Bartley, Bryan; Markeloff, Richard; Mitchell, Tom; Nguyen, Tramy; Sumorok, Daniel; Walczak, Nicholas; Myers, Chris; Zundel, Zach; Hatch, Benjamin; Scholz, James; Colonna-Romano, JohnWe describe an experimental campaign that replicated the performance assessment of logic gates engineered into cells of Saccharomyces cerevisiae by Gander et al. Our experimental campaign used a novel high-throughput experimentation framework developed under Defense Advanced Research Projects Agency’s Synergistic Discovery and Design program: a remote robotic lab at Strateos executed a parameterized experimental protocol. Using this protocol and robotic execution, we generated two orders of magnitude more flow cytometry data than the original experiments. We discuss our results, which largely, but not completely, agree with the original report and make some remarks about lessons learned.Item Determining the biomechanical response of a filiform hair array : a low Reynolds number fluid-structure model(Montana State University - Bozeman, College of Letters & Science, 2009) Cummins, Breschine; Chairperson, Graduate Committee: Tomas GedeonA model system that has been the subject of many anatomical, developmental, functional, and theoretical studies over the last 30 years is the cercal sensory system of the cricket. This system is composed of two antenna-like appendages covered with hundreds of filiform mechanosensory hairs, and encodes information about the direction and dynamics of low-velocity air currents. The encoding is determined by the biomechanical properties of the mechanosensory hairs. These properties are poorly understood, primarily because accurate experimental measurements of the air-current-driven movements of the hairs are difficult to obtain, and adequate mathematical tools for modeling arbitrarily complex hair-to-hair interactions within the canopy have been absent. The study presented here solves fundamental problems in both of these areas. Previous studies have characterized the biomechanics of the filiform hairs, but only one study considered the fluid-mediated interaction of closely-packed hairs. A major goal of our work was to model the motion of a dense patch of thin filaments driven by bulk fluid flow, in a context that is immediately relevant to the cercal system. To understand the function of the sensory epithelium as a whole, we developed a numerical model based on a novel mathematical tool: the method of regularized unsteady Stokeslets. This method is generally applicable to low Reynolds number fluid flow in domains that are subject to periodic forcing along the boundary. The numerical scheme associated with our mathematical model is fast, scalable, accounts for the interaction between arbitrary arrangements of hairs. We measured the biomechanical stimulus-response properties of 19 filiform hairs, and used that data to fit parameters to our mathematical model. We demonstrate for the first time that one of the mechanical parameters controlling filiform hair motion depends on the frequency of the air stimulus. Our numerical simulations demonstrate that damped and synergistic hair interactions can occur between closely-packed hairs. Low frequency signals (< 50 Hz) are damped, and higher frequency signals (50-200 Hz) are amplified. We hypothesize that the characteristic dense patch of hairs at the proximal end of the cercus acts as a noise cancellation filter that removes low frequency components of ambient environmental stimuli.