Distributed gene clinical decision support system based on cloud computing

Background: The clinical decision support system can effectively break the limitations of doctors’ knowledge and reduce the possibility of misdiagnosis to enhance health care. The traditional genetic data storage and analysis methods based on stand-alone environment are hard to meet the computational requirements with the rapid genetic data growth for the limited scalability. Methods: In this paper, we propose a distributed gene clinical decision support system, which is named GCDSS. And a prototype is implemented based on cloud computing technology. At the same time, we present CloudBWA which is a novel distributed read mapping algorithm leveraging batch processing strategy to map reads on Apache Spark. Results: Experiments show that the distributed gene clinical decision support system GCDSS and the distributed read mapping algorithm CloudBWA have outstanding performance and excellent scalability. Compared with state-of-the-art distributed algorithms, CloudBWA achieves up to 2.63 times speedup over SparkBWA. Compared with stand-alone algorithms, CloudBWA with 16 cores achieves up to 11.59 times speedup over BWA-MEM with 1 core. Conclusions: GCDSS is a distributed gene clinical decision support system based on cloud computing techniques. In particular, we incorporated a distributed genetic data analysis pipeline framework in the proposed GCDSS system. To boost the data processing of GCDSS, we propose CloudBWA, which is a novel distributed read mapping algorithm to leverage batch processing technique in mapping stage using Apache Spark platform. Keywords: Clinical decision support system, Cloud computing, Spark, Alluxio, Genetic data analysis, Read mappin

Genome-scale MicroRNA target prediction through clustering with Dirichlet process mixture model

Background: MicroRNA regulation is fundamentally responsible for fine-tuning the whole gene network in human and has been implicated in most physiological and pathological conditions. Studying regulatory impact of microRNA on various cellular and disease processes has resulted in numerous computational tools that investigate microRNA-mRNA interactions through the prediction of static binding site highly dependent on sequence pairing. However, what hindered the practical use of such target prediction is the interplay between competing and cooperative microRNA binding that complicates the whole regulatory process exceptionally. Results: We developed a new method for improved microRNA target prediction based on Dirichlet Process Gaussian Mixture Model (DPGMM) using a large collection of molecular features associated with microRNA, mRNA, and the interaction sites. Multiple validations based on microRNA-mRNA interactions reported in recent large-scale sequencing analyses and a screening test on the entire human transcriptome show that our model outperformed several state-of-the-art tools in terms of promising predictive power on binding sites specific to transcript isoforms with reduced false positive prediction. Last, we illustrated the use of predicted targets in constructing conditional microRNA-mediated gene regulation networks in human cancer. Conclusion: The probability-based binding site prediction provides not only a useful tool for differentiating microRNA targets according to the estimated binding potential but also a capability highly important for exploring dynamic regulation where binding competition is involved

Stacking-ac4C: an ensemble model using mixed features for identifying n4-acetylcytidine in mRNA

N4-acetylcytidine (ac4C) is a modification of cytidine at the nitrogen-4 position, playing a significant role in the translation process of mRNA. However, the precise mechanism and details of how ac4C modifies translated mRNA remain unclear. Since identifying ac4C sites using conventional experimental methods is both labor-intensive and time-consuming, there is an urgent need for a method that can promptly recognize ac4C sites. In this paper, we propose a comprehensive ensemble learning model, the Stacking-based heterogeneous integrated ac4C model, engineered explicitly to identify ac4C sites. This innovative model integrates three distinct feature extraction methodologies: Kmer, electron-ion interaction pseudo-potential values (PseEIIP), and pseudo-K-tuple nucleotide composition (PseKNC). The model also incorporates the robust Cluster Centroids algorithm to enhance its performance in dealing with imbalanced data and alleviate underfitting issues. Our independent testing experiments indicate that our proposed model improves the Mcc by 15.61% and the ROC by 5.97% compared to existing models. To test our model’s adaptability, we also utilized a balanced dataset assembled by the authors of iRNA-ac4C. Our model showed an increase in Sn of 4.1%, an increase in Acc of nearly 1%, and ROC improvement of 0.35% on this balanced dataset. The code for our model is freely accessible at https://github.com/louliliang/ST-ac4C.git, allowing users to quickly build their model without dealing with complicated mathematical equations

A comprehensive study of mobility functioning information in clinical notes: Entity hierarchy, corpus annotation, and sequence labeling

Background Secondary use of Electronic Health Records (EHRs) has mostly focused on health conditions (diseases and drugs). Function is an important health indicator in addition to morbidity and mortality. Nevertheless, function has been overlooked in accessing patients’ health status. The World Health Organization (WHO)’s International Classification of Functioning, Disability and Health (ICF) is considered the international standard for describing and coding function and health states. We pioneer the first comprehensive analysis and identification of functioning concepts in the Mobility domain of the ICF. Results Using physical therapy notes at the National Institutes of Health’s Clinical Center, we induced a hierarchical order of mobility-related entities including 5 entities types, 3 relations, 8 attributes, and 33 attribute values. Two domain experts manually curated a gold standard corpus of 14,281 nested entity mentions from 400 clinical notes. Inter-annotator agreement (IAA) of exact matching averaged 92.3 % F1-score on mention text spans, and 96.6 % Cohen’s kappa on attributes assignments. A high-performance Ensemble machine learning model for named entity recognition (NER) was trained and evaluated using the gold standard corpus. Average F1-score on exact entity matching of our Ensemble method (84.90 %) outperformed popular NER methods: Conditional Random Field (80.4 %), Recurrent Neural Network (81.82 %), and Bidirectional Encoder Representations from Transformers (82.33 %). Conclusions The results of this study show that mobility functioning information can be reliably captured from clinical notes once adequate resources are provided for sequence labeling methods. We expect that functioning concepts in other domains of the ICF can be identified in similar fashion

Modeling antibiotic resistance in the microbiota using Multi-level Petri Nets

Background The unregulated use of antibiotics not only in clinical practice but also in farm animals breeding is causing a unprecedented growth of antibiotic resistant bacterial strains. This problem can be analyzed at different levels, from the antibiotic resistance spreading dynamics at the host population level down to the molecular mechanisms at the bacteria level. In fact, antibiotic administration policies and practices affect the societal system where individuals developing resistance interact with each other and with the environment. Each individual can be seen as a meta-organism together with its associated microbiota, which proves to have a prominent role in the resistance spreading dynamics. Eventually, in each microbiota, bacterial population dynamics and vertical or horizontal gene transfer events activate cellular and molecular mechanisms for resistance spreading that can also be possible targets for its prevention. Results In this work we show how to use the Nets-Within-Nets formalism to model the dynamics between different antibiotic administration protocols and antibiotic resistance, both at the individuals population and at the single microbiota level. Three application examples are presented to show the flexibility of this approach in integrating heterogeneous information in the same model, a fundamental property when creating computational models complex biological systems. Simulations allow to explicitly take into account timing and stochastic events. Conclusions This work demonstrates how the NWN formalism can be used to efficiently model antibiotic resistance population dynamics at different levels of detail. The proposed modeling approach not only provides a valuable tool for investigating causal, quantitative relations between different events and mechanisms, but can be also used as a valid support for decision making processes and protocol development

Towards a Personalized Multi-Domain Digital Neurophenotyping Model for the Detection and Treatment of Mood Trajectories

The commercial availability of many real-life smart sensors, wearables, and mobile apps provides a valuable source of information about a wide range of human behavioral, physiological, and social markers that can be used to infer the user’s mental state and mood. However, there are currently no commercial digital products that integrate these psychosocial metrics with the real-time measurement of neural activity. In particular, electroencephalography (EEG) is a well-validated and highly sensitive neuroimaging method that yields robust markers of mood and affective processing, and has been widely used in mental health research for decades. The integration of wearable neuro-sensors into existing multimodal sensor arrays could hold great promise for deep digital neurophenotyping in the detection and personalized treatment of mood disorders. In this paper, we propose a multi-domain digital neurophenotyping model based on the socioecological model of health. The proposed model presents a holistic approach to digital mental health, leveraging recent neuroscientific advances, and could deliver highly personalized diagnoses and treatments. The technological and ethical challenges of this model are discussed

Temporal decision making using unsupervised learning

With the explosion of ubiquitous continuous sensing, on-line streaming clustering continues to attract attention. The requirements are that the streaming clustering algorithm recognize and adapt clusters as the data evolves, that anomalies are detected, and that new clusters are automatically formed as incoming data dictate. In this dissertation, we develop a streaming clustering algorithm, MU Streaming Clustering (MUSC), that is based on coupling a Gaussian mixture model (GMM) with possibilistic clustering to build an adaptive system for analyzing streaming multi-dimensional activity feature vectors. For this reason, the possibilistic C-Means (PCM) and Automatic Merging Possibilistic Clustering Method (AMPCM) are combined together to cluster the initial data points, detect anomalies and initialize the GMM. MUSC achieves our goals when tested on synthetic and real-life datasets. We also compare MUSC's performance with Sequential k-means (sk-means), Basic Sequential Clustering Algorithm (BSAS), and Modified BSAS (MBSAS) here MUSC shows superiority in the performance and accuracy. The performance of a streaming clustering algorithm needs to be monitored over time to understand the behavior of the streaming data in terms of new emerging clusters and number of outlier data points. Incremental internal Validity Indices (iCVIs) are used to monitor the performance of an on-line clustering algorithm. We study the internal incremental Davies-Bouldin (DB), Xie-Beni (XB), and Dunn internal cluster validity indices in the context of streaming data analysis. We extend the original incremental DB (iDB) to a more general version parameterized by the exponent of membership weights. Then we illustrate how the iDB can be used to analyze and understand the performance of MUSC algorithm. We give examples that illustrate the appearance of a new cluster, the effect of different cluster sizes, handling of outlier data samples, and the effect of the input order on the resultant cluster history. In addition, we investigate the internal incremental Davies-Bouldin (iDB) cluster validity index in the context of big streaming data analysis. We analyze the effect of large numbers of samples on the values of the iCVI (iDB). We also develop online versions of two modified generalized Dunn's indices that can be used for dynamic evaluation of evolving (cluster) structure in streaming data. We argue that this method is a good way to monitor the ongoing performance of online clustering algorithms and we illustrate several types of inferences that can be drawn from such indices. We compare the two new indices to the incremental Xie-Beni and Davies-Bouldin indices, which to our knowledge offer the only comparable approach, with numerical examples on a variety of synthetic and real data sets. We also study the performance of MUSC and iCVIs with big streaming data applications. We show the advantage of iCVIs in monitoring large streaming datasets and in providing useful information about the data stream in terms of emergence of a new structure, amount of outlier data, size of the clusters, and order of data samples in each cluster. We also propose a way to project streaming data into a lower space for cases where the distance measure does not perform as expected in the high dimensional space. Another example of streaming is the data acivity data coming from TigerPlace and other elderly residents' apartments in and around Columbia. MO. TigerPlace is an eldercare facility that promotes aging-in-place in Columbia Missouri. Eldercare monitoring using non-wearable sensors is a candidate solution for improving care and reducing costs. Abnormal sensor patterns produced by certain resident behaviors could be linked to early signs of illness. We propose an unsupervised method for detecting abnormal behavior patterns based on a new context preserving representation of daily activities. A preliminary analysis of the method was conducted on data collected in TigerPlace. Sensor firings of each day are converted into sequences of daily activities. Then, building a histogram from the daily sequences of a resident, we generate a single data vector representing that day. Using the proposed method, a day with hundreds of sequences is converted into a single data point representing that day and preserving the context of the daily routine at the same time. We obtained an average Area Under the Curve (AUC) of 0.9 in detecting days where elder adults need to be assessed. Our approach outperforms other approaches on the same datset. Using the context preserving representation, we develoed a multi-dimensional alert system to improve the existing single-dimensional alert system in TigerPlace. Also, this represenation is used to develop a framework that utilizes sensor sequence similarity and medical concepts extracted from the EHR to automatically inform the nursing staff when health problems are detected. Our context preserving representation of daily activities is used to measure the similarity between the sensor sequences of different days. The medical concepts are extracted from the nursing notes using MetamapLite, an NLP tool included in the Unified Medical Language System (UMLS). The proposed idea is validated on two pilot datasets from twelve Tiger Place residents, with a total of 5810 sensor days out of which 1966 had nursing notes

Query-Constraint-Based Mining of Association Rules for Exploratory Analysis of Clinical Datasets in the National Sleep Research Resource

Background: Association Rule Mining (ARM) has been widely used by biomedical researchers to perform exploratory data analysis and uncover potential relationships among variables in biomedical datasets. However, when biomedical datasets are high-dimensional, performing ARM on such datasets will yield a large number of rules, many of which may be uninteresting. Especially for imbalanced datasets, performing ARM directly would result in uninteresting rules that are dominated by certain variables that capture general characteristics. Methods: We introduce a query-constraint-based ARM (QARM) approach for exploratory analysis of multiple, diverse clinical datasets in the National Sleep Research Resource (NSRR). QARM enables rule mining on a subset of data items satisfying a query constraint. We first perform a series of data-preprocessing steps including variable selection, merging semantically similar variables, combining multiple-visit data, and data transformation. We use Top-k Non-Redundant (TNR) ARM algorithm to generate association rules. Then we remove general and subsumed rules so that unique and non-redundant rules are resulted for a particular query constraint. Results: Applying QARM on five datasets from NSRR obtained a total of 2517 association rules with a minimum confidence of 60% (using top 100 rules for each query constraint). The results show that merging similar variables could avoid uninteresting rules. Also, removing general and subsumed rules resulted in a more concise and interesting set of rules. Conclusions: QARM shows the potential to support exploratory analysis of large biomedical datasets. It is also shown as a useful method to reduce the number of uninteresting association rules generated from imbalanced datasets. A preliminary literature-based analysis showed that some association rules have supporting evidence from biomedical literature, while others without literature-based evidence may serve as the candidates for new hypotheses to explore and investigate. Together with literature-based evidence, the association rules mined over the NSRR clinical datasets may be used to support clinical decisions for sleep-related problems

Transfer learning for Alzheimer’s disease through neuroimaging biomarkers: A systematic review

Producción CientíficaAlzheimer’s disease (AD) is a remarkable challenge for healthcare in the 21st century. Since 2017, deep learning models with transfer learning approaches have been gaining recognition in AD detection, and progression prediction by using neuroimaging biomarkers. This paper presents a systematic review of the current state of early AD detection by using deep learning models with transfer learning and neuroimaging biomarkers. Five databases were used and the results before screening report 215 studies published between 2010 and 2020. After screening, 13 studies met the inclusion criteria. We noted that the maximum accuracy achieved to date for AD classification is 98.20% by using the combination of 3D convolutional networks and local transfer learning, and that for the prognostic prediction of AD is 87.78% by using pre-trained 3D convolutional network-based architectures. The results show that transfer learning helps researchers in developing a more accurate system for the early diagnosis of AD. However, there is a need to consider some points in future research, such as improving the accuracy of the prognostic prediction of AD, exploring additional biomarkers such as tau-PET and amyloid-PET to understand highly discriminative feature representation to separate similar brain patterns, managing the size of the datasets due to the limited availability.Ministerio de Industria, Energía y Turismo (AAL-20125036