Validating dynamicity in resting state fMRI with activation-informed temporal segmentation.

Confirming the presence (or absence) of dynamic functional connectivity (dFC) states during rest is an important open question in the field of cognitive neuroscience. The prevailing dFC framework aims to identify dynamics directly from connectivity estimates with a sliding window approach, however this method suffers from several drawbacks including sensitivity to window size and poor test-retest reliability. We hypothesize that time-varying changes in functional connectivity are mirrored by significant temporal changes in functional activation, and that this coupling can be leveraged to study dFC without the need for a predefined sliding window. Here, we introduce a data-driven dFC framework, which involves informed segmentation of fMRI time series at candidate FC state transition points estimated from changes in whole-brain functional activation, rather than a fixed-length sliding window. We show our approach reliably identifies true cognitive state change points when applied on block-design working memory task data and outperforms the standard sliding window approach in both accuracy and computational efficiency in this context. When applied to data from four resting state fMRI scanning sessions, our method consistently recovers five reliable FC states, and subject-specific features derived from these states show significant correlation with behavioral phenotypes of interest (cognitive ability, personality). Overall, these results suggest abrupt whole-brain changes in activation can be used as a marker for changes in connectivity states and provides new evidence for the existence of time-varying FC in rest.

Biogeography and environmental conditions shape bacteriophage-bacteria networks across the human microbiome.

Viruses and bacteria are critical components of the human microbiome and play important roles in health and disease. Most previous work has relied on studying bacteria and viruses independently, thereby reducing them to two separate communities. Such approaches are unable to capture how these microbial communities interact, such as through processes that maintain community robustness or allow phage-host populations to co-evolve. We implemented a network-based analytical approach to describe phage-bacteria network diversity throughout the human body. We built these community networks using a machine learning algorithm to predict which phages could infect which bacteria in a given microbiome. Our algorithm was applied to paired viral and bacterial metagenomic sequence sets from three previously published human cohorts. We organized the predicted interactions into networks that allowed us to evaluate phage-bacteria connectedness across the human body. We observed evidence that gut and skin network structures were person-specific and not conserved among cohabitating family members. High-fat diets appeared to be associated with less connected networks. Network structure differed between skin sites, with those exposed to the external environment being less connected and likely more susceptible to network degradation by microbial extinction events. This study quantified and contrasted the diversity of virome-microbiome networks across the human body and illustrated how environmental factors may influence phage-bacteria interactive dynamics. This work provides a baseline for future studies to better understand system perturbations, such as disease states, through ecological networks.

Democratizing EHR analyses with FIDDLE: a flexible data-driven preprocessing pipeline for structured clinical data.

OBJECTIVE: In applying machine learning (ML) to electronic health record (EHR) data, many decisions must be made before any ML is applied; such preprocessing requires substantial effort and can be labor-intensive. As the role of ML in health care grows, there is an increasing need for systematic and reproducible preprocessing techniques for EHR data. Thus, we developed FIDDLE (Flexible Data-Driven Pipeline), an open-source framework that streamlines the preprocessing of data extracted from the EHR. MATERIALS AND METHODS: Largely data-driven, FIDDLE systematically transforms structured EHR data into feature vectors, limiting the number of decisions a user must make while incorporating good practices from the literature. To demonstrate its utility and flexibility, we conducted a proof-of-concept experiment in which we applied FIDDLE to 2 publicly available EHR data sets collected from intensive care units: MIMIC-III and the eICU Collaborative Research Database. We trained different ML models to predict 3 clinically important outcomes: in-hospital mortality, acute respiratory failure, and shock. We evaluated models using the area under the receiver operating characteristics curve (AUROC), and compared it to several baselines. RESULTS: Across tasks, FIDDLE extracted 2,528 to 7,403 features from MIMIC-III and eICU, respectively. On all tasks, FIDDLE-based models achieved good discriminative performance, with AUROCs of 0.757-0.886, comparable to the performance of MIMIC-Extract, a preprocessing pipeline designed specifically for MIMIC-III. Furthermore, our results showed that FIDDLE is generalizable across different prediction times, ML algorithms, and data sets, while being relatively robust to different settings of user-defined arguments. CONCLUSIONS: FIDDLE, an open-source preprocessing pipeline, facilitates applying ML to structured EHR data. By accelerating and standardizing labor-intensive preprocessing, FIDDLE can help stimulate progress in building clinically useful ML tools for EHR data.