Deriving executable models of biochemical network dynamics from qualitative data

Progress in advancing our understanding of biological systems is limited by their sheer complexity, the cost of laboratory materials and equipment, and limitations of current laboratory technology. Computational and mathematical modeling provide ways to address these obstacles through hypothesis generation and testing without experimentation---allowing researchers to analyze system structure and dynamics in silico and, then, design lab experiments that yield desired information about phenomena of interest. These models, however, are only as accurate and complete as the data used to build them. Currently, most models are constructed from quantitative experimental data. However, since accurate quantitative measurements are hard to obtain and difficult to adapt from literature and online databases, new sources of data for building models need to be explored. In my work, I have designed methods for building and executing computational models of cellular network dynamics based on qualitative experimental data, which are more abundant, easier to obtain, and reliably reproducible. Such executable models allow for in silico perturbation, simulation, and exploration of biological systems. In this thesis, I present two general strategies for building and executing tokenized models of biochemical networks using only qualitative data. Both methods have been successfully used to model and predict the dynamics of signaling networks in normal and cancer cell lines, rivaling the accuracy of existing methods trained on quantitative data. I have implemented these methods in the software tools PathwayOracle and Monarch, making the new techniques I present here accessible to experimental biologists and other domain experts in cellular biology

Invasion of Ukraine Discourse on TikTok Dataset

We present a dataset of videos and comments from the social media platform TikTok, centred around the invasion of Ukraine in 2022, an event that launched TikTok into the geopolitical arena. The discourse around the invasion exposed myriad political behaviours and dynamics that are unexplored on this platform. To this end we provide a mass scale language and interaction dataset for further research into these processes. An initial investigation of language and social interaction dynamics are explored in this paper. The dataset and the library used to collect it are open sourced to the public

Challenges When Identifying Migration from Geo-Located Twitter Data

Given the challenges in collecting up-to-date, comparable data on migrant populations the potential of digital trace data to study migration and migrants has sparked considerable interest among researchers and policy makers. In this paper we assess the reliability of one such data source that is heavily used within the research community: geolocated tweets. We assess strategies used in previous work to identify migrants based on their geolocation histories. We apply these approaches to infer the travel history of a set of Twitter users who regularly posted geolocated tweets between July 2012 and June 2015. In a second step we hand-code the entire tweet histories of a subset of the accounts identified as migrants by these methods. Upon close inspection very few of the accounts that are classified as migrants appear to be migrants in any conventional sense or international students. Rather we find these approaches identify other highly mobile populations such as frequent business or leisure travellers, or people who might best be described as “transnationals”. For demographic research that draws on this kind of data to generate estimates of migration flows this high mis-classification rate implies that findings are likely sensitive to the adjustment model used. For most research trying to use these data to study migrant populations, the data will be of limited utility. We suspect that increasing the correct classification rate substantially will not be easy and may introduce other biases

A Method for the Automated, Reliable Retrieval of Publication-Citation Records

BACKGROUND: Publication records and citation indices often are used to evaluate academic performance. For this reason, obtaining or computing them accurately is important. This can be difficult, largely due to a lack of complete knowledge of an individual's publication list and/or lack of time available to manually obtain or construct the publication-citation record. While online publication search engines have somewhat addressed these problems, using raw search results can yield inaccurate estimates of publication-citation records and citation indices. METHODOLOGY: In this paper, we present a new, automated method that produces estimates of an individual's publication-citation record from an individual's name and a set of domain-specific vocabulary that may occur in the individual's publication titles. Because this vocabulary can be harvested directly from a research web page or online (partial) publication list, our method delivers an easy way to obtain estimates of a publication-citation record and the relevant citation indices. Our method works by applying a series of stringent name and content filters to the raw publication search results returned by an online publication search engine. In this paper, our method is run using Google Scholar, but the underlying filters can be easily applied to any existing publication search engine. When compared against a manually constructed data set of individuals and their publication-citation records, our method provides significant improvements over raw search results. The estimated publication-citation records returned by our method have an average sensitivity of 98% and specificity of 72% (in contrast to raw search result specificity of less than 10%). When citation indices are computed using these records, the estimated indices are within of the true value 10%, compared to raw search results which have overestimates of, on average, 75%. CONCLUSIONS: These results confirm that our method provides significantly improved estimates over raw search results, and these can either be used directly for large-scale (departmental or university) analysis or further refined manually to quickly give accurate publication-citation records

Confounding factors in HGT detection: Statistical error, coalescent effects, and multiple solutions

Prokaryotic organisms share genetic material across species boundaries by means of a process known as horizontal gene transfer (HGT). This process has great significance for understanding prokaryotic genome diversification and unraveling their complexities. Phylogeny-based detection of HGT is one of the most commonly used methods for this task, and is based on the fundamental fact that HGT may cause gene trees to disagree with one another, as well as with the species phylogeny. Using these methods, we can compare gene and species trees, and infer a set of HGT events to reconcile the differences among these trees. In this paper, we address three factors that confound the detection of the true HGT events, including the donors and recipients of horizontally transferred genes. First, we study experimentally the effects of error in the estimated gene trees (statistical error) on the accuracy of inferred HGT events. Our results indicate that statistical error leads to overestimation of the number of HGT events, and that HGT detection methods should be designed with unresolved gene trees in mind. Second, we demonstrate, both theoretically and empirically, that based on topological comparison alone, the number of HGT scenarios that reconcile a pair of species/gene trees may be exponential. This number may be reduced when branch lengths in both trees are estimated correctly. This set of results implies that in the absence of additional biological information, and/or a biological model of how HGT occurs, multiple HGT scenarios must be sought, and efficient strategies for how to enumerate such solutions must be developed. Third, we address the issue of lineage sorting, how it confounds HGT detection, and how to incorporate it with HGT into a single stochastic framework that distinguishes between the two events by extending population genetics theories. This result is very important, particularly when analyzing closely related organisms, where coalescent effects may not be ignored when reconciling gene trees. In addition to these three confounding factors, we consider the problem of enumerating all valid coalescent scenarios that constitute plausible species/gene tree reconciliations, and develop a polynomial-time dynamic programming algorithm for solving it. This result bears great significance on reducing the search space for heuristics that seek reconciliation scenarios. Finally, we show, empirically, that the locality of incongruence between a pair of trees has an impact on the numbers of HGT and coalescent reconciliation scenarios