Assessment of symptom severity in psychotic disorder patients based on heart rate variability and accelerometer mobility data.

BACKGROUND: Advancement in mental health care requires easily accessible, efficient diagnostic and treatment assessment tools. Viable biomarkers could enable objectification and automation of the diagnostic and treatment process, currently dependent on a psychiatric interview. Available wearable technology and computational methods make it possible to incorporate heart rate variability (HRV), an indicator of autonomic nervous system (ANS) activity, into potential diagnostic and treatment assessment frameworks as a biomarker of disease severity in mental disorders, including schizophrenia and bipolar disorder (BD). METHOD: We used a commercially available electrocardiography (ECG) chest strap with a built-in accelerometer, i.e. Polar H10, to record R-R intervals and physical activity of 30 hospitalized schizophrenia or BD patients and 30 control participants through ca. 1.5-2 h time periods. We validated a novel approach to data acquisition based on a flexible, patient-friendly and cost-effective setting. We analyzed the relationship between HRV and the Positive and Negative Syndrome Scale (PANSS) test scores, as well as the HRV and mobility coefficient. We also proposed a method of rest period selection based on R-R intervals and mobility data. The source code for reproducing all experiments is available on GitHub, while the dataset is published on Zenodo. RESULTS: Mean HRV values were lower in the patient compared to the control group and negatively correlated with the results of the PANSS general subcategory. For the control group, we also discovered the inversely proportional dependency between the mobility coefficient, based on accelerometer data, and HRV. This relationship was less pronounced for the treatment group. CONCLUSIONS: HRV value itself, as well as the relationship between HRV and mobility, may be promising biomarkers in disease diagnostics. These findings can be used to develop a flexible monitoring system for symptom severity assessment.

Modified linear regression predicts drug-target interactions accurately.

State-of-the-art approaches for the prediction of drug-target interactions (DTI) are based on various techniques, such as matrix factorisation, restricted Boltzmann machines, network-based inference and bipartite local models (BLM). In this paper, we propose the framework of Asymmetric Loss Models (ALM) which is more consistent with the underlying chemical reality compared with conventional regression techniques. Furthermore, we propose to use an asymmetric loss model with BLM to predict drug-target interactions accurately. We evaluate our approach on publicly available real-world drug-target interaction datasets. The results show that our approach outperforms state-of-the-art DTI techniques, including recent versions of BLM.

Resting State fMRI Functional Connectivity-Based Classification Using a Convolutional Neural Network Architecture.

Machine learning techniques have become increasingly popular in the field of resting state fMRI (functional magnetic resonance imaging) network based classification. However, the application of convolutional networks has been proposed only very recently and has remained largely unexplored. In this paper we describe a convolutional neural network architecture for functional connectome classification called connectome-convolutional neural network (CCNN). Our results on simulated datasets and a publicly available dataset for amnestic mild cognitive impairment classification demonstrate that our CCNN model can efficiently distinguish between subject groups. We also show that the connectome-convolutional network is capable to combine information from diverse functional connectivity metrics and that models using a combination of different connectivity descriptors are able to outperform classifiers using only one metric. From this flexibility follows that our proposed CCNN model can be easily adapted to a wide range of connectome based classification or regression tasks, by varying which connectivity descriptor combinations are used to train the network.

Drug-target interaction prediction: A Bayesian ranking approach.

BACKGROUND AND OBJECTIVE: In silico prediction of drug-target interactions (DTI) could provide valuable information and speed-up the process of drug repositioning - finding novel usage for existing drugs. In our work, we focus on machine learning algorithms supporting drug-centric repositioning approach, which aims to find novel usage for existing or abandoned drugs. We aim at proposing a per-drug ranking-based method, which reflects the needs of drug-centric repositioning research better than conventional drug-target prediction approaches. METHODS: We propose Bayesian Ranking Prediction of Drug-Target Interactions (BRDTI). The method is based on Bayesian Personalized Ranking matrix factorization (BPR) which has been shown to be an excellent approach for various preference learning tasks, however, it has not been used for DTI prediction previously. In order to successfully deal with DTI challenges, we extended BPR by proposing: (i) the incorporation of target bias, (ii) a technique to handle new drugs and (iii) content alignment to take structural similarities of drugs and targets into account. RESULTS: Evaluation on five benchmark datasets shows that BRDTI outperforms several state-of-the-art approaches in terms of per-drug nDCG and AUC. BRDTI results w.r.t. nDCG are 0.929, 0.953, 0.948, 0.897 and 0.690 for G-Protein Coupled Receptors (GPCR), Ion Channels (IC), Nuclear Receptors (NR), Enzymes (E) and Kinase (K) datasets respectively. Additionally, BRDTI significantly outperformed other methods (BLM-NII, WNN-GIP, NetLapRLS and CMF) w.r.t. nDCG in 17 out of 20 cases. Furthermore, BRDTI was also shown to be able to predict novel drug-target interactions not contained in the original datasets. The average recall at top-10 predicted targets for each drug was 0.762, 0.560, 1.000 and 0.404 for GPCR, IC, NR, and E datasets respectively. CONCLUSIONS: Based on the evaluation, we can conclude that BRDTI is an appropriate choice for researchers looking for an in silico DTI prediction technique to be used in drug-centric repositioning scenarios. BRDTI Software and supplementary materials are available online at www.ksi.mff.cuni.cz/∼peska/BRDTI.

Resting State fMRI Functional Connectivity Analysis Using Dynamic Time Warping.

Traditional resting-state network concept is based on calculating linear dependence of spontaneous low frequency fluctuations of the BOLD signals of different brain areas, which assumes temporally stable zero-lag synchrony across regions. However, growing amount of experimental findings suggest that functional connectivity exhibits dynamic changes and a complex time-lag structure, which cannot be captured by the static zero-lag correlation analysis. Here we propose a new approach applying Dynamic Time Warping (DTW) distance to evaluate functional connectivity strength that accounts for non-stationarity and phase-lags between the observed signals. Using simulated fMRI data we found that DTW captures dynamic interactions and it is less sensitive to linearly combined global noise in the data as compared to traditional correlation analysis. We tested our method using resting-state fMRI data from repeated measurements of an individual subject and showed that DTW analysis results in more stable connectivity patterns by reducing the within-subject variability and increasing robustness for preprocessing strategies. Classification results on a public dataset revealed a superior sensitivity of the DTW analysis to group differences by showing that DTW based classifiers outperform the zero-lag correlation and maximal lag cross-correlation based classifiers significantly. Our findings suggest that analysing resting-state functional connectivity using DTW provides an efficient new way for characterizing functional networks.

Classification of gene expression data: A hubness-aware semi-supervised approach.

BACKGROUND AND OBJECTIVE: Classification of gene expression data is the common denominator of various biomedical recognition tasks. However, obtaining class labels for large training samples may be difficult or even impossible in many cases. Therefore, semi-supervised classification techniques are required as semi-supervised classifiers take advantage of unlabeled data. METHODS: Gene expression data is high-dimensional which gives rise to the phenomena known under the umbrella of the curse of dimensionality, one of its recently explored aspects being the presence of hubs or hubness for short. Therefore, hubness-aware classifiers have been developed recently, such as Naive Hubness-Bayesian k-Nearest Neighbor (NHBNN). In this paper, we propose a semi-supervised extension of NHBNN which follows the self-training schema. As one of the core components of self-training is the certainty score, we propose a new hubness-aware certainty score. RESULTS: We performed experiments on publicly available gene expression data. These experiments show that the proposed classifier outperforms its competitors. We investigated the impact of each of the components (classification algorithm, semi-supervised technique, hubness-aware certainty score) separately and showed that each of these components are relevant to the performance of the proposed approach. CONCLUSIONS: Our results imply that our approach may increase classification accuracy and reduce computational costs (i.e., runtime). Based on the promising results presented in the paper, we envision that hubness-aware techniques will be used in various other biomedical machine learning tasks. In order to accelerate this process, we made an implementation of hubness-aware machine learning techniques publicly available in the PyHubs software package (http://www.biointelligence.hu/pyhubs) implemented in Python, one of the most popular programming languages of data science.

RECORD: Reference-Assisted Genome Assembly for Closely Related Genomes.

Background. Next-generation sequencing technologies are now producing multiple times the genome size in total reads from a single experiment. This is enough information to reconstruct at least some of the differences between the individual genome studied in the experiment and the reference genome of the species. However, in most typical protocols, this information is disregarded and the reference genome is used. Results. We provide a new approach that allows researchers to reconstruct genomes very closely related to the reference genome (e.g., mutants of the same species) directly from the reads used in the experiment. Our approach applies de novo assembly software to experimental reads and so-called pseudoreads and uses the resulting contigs to generate a modified reference sequence. In this way, it can very quickly, and at no additional sequencing cost, generate new, modified reference sequence that is closer to the actual sequenced genome and has a full coverage. In this paper, we describe our approach and test its implementation called RECORD. We evaluate RECORD on both simulated and real data. We made our software publicly available on sourceforge. Conclusion. Our tests show that on closely related sequences RECORD outperforms more general assisted-assembly software.

A Specialized Histone H1 Variant Is Required for Adaptive Responses to Complex Abiotic Stress and Related DNA Methylation in Arabidopsis.

Linker (H1) histones play critical roles in chromatin compaction in higher eukaryotes. They are also the most variable of the histones, with numerous nonallelic variants cooccurring in the same cell. Plants contain a distinct subclass of minor H1 variants that are induced by drought and abscisic acid and have been implicated in mediating adaptive responses to stress. However, how these variants facilitate adaptation remains poorly understood. Here, we show that the single Arabidopsis (Arabidopsis thaliana) stress-inducible variant H1.3 occurs in plants in two separate and most likely autonomous pools: a constitutive guard cell-specific pool and a facultative environmentally controlled pool localized in other tissues. Physiological and transcriptomic analyses of h1.3 null mutants demonstrate that H1.3 is required for both proper stomatal functioning under normal growth conditions and adaptive developmental responses to combined light and water deficiency. Using fluorescence recovery after photobleaching analysis, we show that H1.3 has superfast chromatin dynamics, and in contrast to the main Arabidopsis H1 variants H1.1 and H1.2, it has no stable bound fraction. The results of global occupancy studies demonstrate that, while H1.3 has the same overall binding properties as the main H1 variants, including predominant heterochromatin localization, it differs from them in its preferences for chromatin regions with epigenetic signatures of active and repressed transcription. We also show that H1.3 is required for a substantial part of DNA methylation associated with environmental stress, suggesting that the likely mechanism underlying H1.3 function may be the facilitation of chromatin accessibility by direct competition with the main H1 variants.