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Research synthesis on simple yet general hypotheses and ideas is challenging in scientific disciplines studying highly context-dependent systems such as medical, social, and biological sciences. This study shows that machine learning, equation-free statistical modeling of artificial intelligence, is a promising synthesis tool for discovering novel patterns and the source of controversy in a general hypothesis. We apply a decision tree algorithm, assuming that evidence from various contexts can be adequately integrated in a hierarchically nested structure. As a case study, we analyzed 163 articles that studied a prominent hypothesis in invasion biology, the enemy release hypothesis. We explored if any of the nine attributes that classify each study can differentiate conclusions as classification problem. Results corroborated that machine learning can be useful for research synthesis, as the algorithm could detect patterns that had been already focused in previous narrative reviews. Compared with the previous synthesis study that assessed the same evidence collection based on experts' judgement, the algorithm has newly proposed that the studies focusing on Asian regions mostly supported the hypothesis, suggesting that more detailed investigations in these regions can enhance our understanding of the hypothesis. We suggest that machine learning algorithms can be a promising synthesis tool especially where studies (a) reformulate a general hypothesis from different perspectives, (b) use different methods or variables, or (c) report insufficient information for conducting meta-analyses.
Since half a century, cytometry has been a major scientific discipline in the field of cytomics - the study of system’s biology at single cell level. It enables the investigation of physiological processes, functional characteristics and rare events with proteins by analysing multiple parameters on an individual cell basis. In the last decade, mass cytometry has been established which increased the parallel measurement to up to 50 proteins. This has shifted the analysis strategy from conventional consecutive manual gates towards multi-dimensional data processing. Novel algorithms have been developed to tackle these high-dimensional protein combinations in the data. They are mainly based on clustering or non-linear dimension reduction techniques, or both, often combined with an upstream downsampling procedure. However, these tools have obstacles either in comprehensible interpretability, reproducibility, computational complexity or in comparability between samples and groups.
To address this bottleneck, a reproducible, semi-automated cytometric data mining workflow PRI (pattern recognition of immune cells) is proposed which combines three main steps: i) data preparation and storage; ii) bin-based combinatorial variable engineering of three protein markers, the so called triploTs, and subsequent sectioning of these triploTs in four parts; and iii) deployment of a data-driven supervised learning algorithm, the cross-validated elastic-net regularized logistic regression, with these triploT sections as input variables. As a result, the selected variables from the models are ranked by their prevalence, which potentially have discriminative value. The purpose is to significantly facilitate the identification of meaningful subpopulations, which are most distinguish between two groups. The proposed workflow PRI is exemplified by a recently published public mass cytometry data set. The authors found a T cell subpopulation which is discriminative between effective and ineffective treatment of breast carcinomas in mice. With PRI, that subpopulation was not only validated, but was further narrowed down as a particular Th1 cell population. Moreover, additional insights of combinatorial protein expressions are revealed in a traceable manner. An essential element in the workflow is the reproducible variable engineering. These variables serve as basis for a clearly interpretable visualization, for a structured variable exploration and as input layers in neural network constructs.
PRI facilitates the determination of marker levels in a semi-continuous manner. Jointly with the combinatorial display, it allows a straightforward observation of correlating patterns, and thus, the dominant expressed markers and cell hierarchies. Furthermore, it enables the identification and complex characterization of discriminating subpopulations due to its reproducible and pseudo-multi-parametric pattern presentation. This endorses its applicability as a tool for unbiased investigations on cell subsets within multi-dimensional cytometric data sets.