A Hybrid of Metabolic Flux Analysis and Bayesian Factor Modeling for Multiomic Temporal Pathway Activation.

The growing availability of multiomic data provides a highly comprehensive view of cellular processes at the levels of mRNA, proteins, metabolites, and reaction fluxes. However, due to probabilistic interactions between components depending on the environment and on the time course, casual, sometimes rare interactions may cause important effects in the cellular physiology. To date, interactions at the pathway level cannot be measured directly, and methodologies to predict pathway cross-correlations from reaction fluxes are still missing. Here, we develop a multiomic approach of flux-balance analysis combined with Bayesian factor modeling with the aim of detecting pathway cross-correlations and predicting metabolic pathway activation profiles. Starting from gene expression profiles measured in various environmental conditions, we associate a flux rate profile with each condition. We then infer pathway cross-correlations and identify the degrees of pathway activation with respect to the conditions and time course using Bayesian factor modeling. We test our framework on the most recent metabolic reconstruction of Escherichia coli in both static and dynamic environments, thus predicting the functionality of particular groups of reactions and how it varies over time. In a dynamic environment, our method can be readily used to characterize the temporal progression of pathway activation in response to given stimuli

Cogena, a novel tool for co-expressed gene-set enrichment analysis, applied to drug repositioning and drug mode of action discovery

This work was supported by the portfolio of translational research of the National Institutes for Health Research Cardiovascular Biomedical Research Unit at Barts, the UK Medical Research Council (JID-2015-0339), Major Research Plan of The National Natural Science Foundation of China [grant number U1435222], Plan for Innovative Graduate Student at NUDT [grant number B140202], Plan for interdisciplinary joint PhD students at NUDT and China Scholarship Council [to ZJ]

Selecting the Most Important Features for Predicting Mild Cognitive Impairment from Thai Verbal Fluency Assessments

Mild cognitive impairment (MCI) is an early stage of cognitive decline or memory loss, commonly found among the elderly. A phonemic verbal fluency (PVF) task is a standard cognitive test that participants are asked to produce words starting with given letters, such as “F” in English and “ก” /k/ in Thai. With state-of-the-art machine learning techniques, features extracted from the PVF data have been widely used to detect MCI. The PVF features, including acoustic features, semantic features, and word grouping, have been studied in many languages but not Thai. However, applying the same PVF feature extraction methods used in English to Thai yields unpleasant results due to different language characteristics. This study performs analytical feature extraction on Thai PVF data to classify MCI patients. In particular, we propose novel approaches to extract features based on phonemic clustering (ability to cluster words by phonemes) and switching (ability to shift between clusters) for the Thai PVF data. The comparison results of the three classifiers revealed that the support vector machine performed the best with an area under the receiver operating characteristic curve (AUC) of 0.733 (N = 100). Furthermore, our implemented guidelines extracted efficient features, which support the machine learning models regarding MCI detection on Thai PVF data

Using Automatic Speech Recognition to Assess Thai Speech Language Fluency in the Montreal Cognitive Assessment (MoCA)

The Montreal cognitive assessment (MoCA), a widely accepted screening tool for identifying patients with mild cognitive impairment (MCI), includes a language fluency test of verbal functioning; its scores are based on the number of unique correct words produced by the test taker. However, it is possible that unique words may be counted differently for various languages. This study focuses on Thai as a language that differs from English in terms of word combinations. We applied various automatic speech recognition (ASR) techniques to develop an assisted scoring system for the MoCA language fluency test with Thai language support. This was a challenge because Thai is a low-resource language for which domain-specific data are not publicly available, especially speech data from patients with MCIs. Furthermore, the great variety of pronunciation, intonation, tone, and accent of the patients, all of which might differ from healthy controls, bring more complexity to the model. We propose a hybrid time delay neural network hidden Markov model (TDNN-HMM) architecture for acoustic model training to create our ASR system that is robust to environmental noise and to the variation of voice quality impacted by MCI. The LOTUS Thai speech corpus was incorporated into the training set to improve the model’s generalization. A preprocessing algorithm was implemented to reduce the background noise and improve the overall data quality before feeding data into the TDNN-HMM system for automatic word detection and language fluency score calculation. The results show that the TDNN-HMM model in combination with data augmentation using lattice-free maximum mutual information (LF-MMI) objective function provides a word error rate (WER) of 30.77%. To our knowledge, this is the first study to develop an ASR with Thai language support to automate the scoring system of MoCA’s language fluency assessment

Identification of differential RNA modifications from nanopore direct RNA sequencing with xPore

10.1038/s41587-021-00949-wNATURE BIOTECHNOLOGY391