BioMedInformatics, Volume 1, Issue 3 (December 2021) – 8 articles

Modern network science has been used to reveal new and often fundamental aspects of brain network organization in physiological as well as pathological conditions. As a consequence, these discoveries, which relate to network hierarchy, hubs and network interactions, have begun to change the paradigms of neurodegenerative disorders. In this paper, we explore the use of thermodynamics for protein–protein network interactions in Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), traumatic brain injury and epilepsy. To assess the validity of using network interactions in neurological diseases, we investigated the relationship between network thermodynamics and molecular systems biology for these neurological disorders. In order to uncover whether there was a correlation between network organization and biological outcomes, we used publicly available RNA transcription data from individual patients with these neurological conditions, and correlated these molecular profiles with their respective individual disability scores. We found a linear correlation (Pearson correlation of −0.828) between disease disability (a clinically validated measurement of a person’s functional status) and Gibbs free energy (a thermodynamic measure of protein–protein interactions). In other words, we found an inverse relationship between disease disability and thermodynamic energy. Because a larger degree of disability correlated with a larger negative drop in Gibbs free energy in a linear disability-dependent fashion, it could be presumed that the progression of neuropathology such as is seen in Alzheimer’s disease could potentially be prevented by therapeutically correcting the changes in Gibbs free energy. Full article

According to the WHO, approximately 50 million people worldwide have dementia and there are nearly 10 million new cases every year. Alzheimer’s disease is the most common form of dementia and may contribute to 60–70% of cases. It has been proved that early diagnosis is key to promoting early and optimal management. However, the early stage of dementia is often overlooked and patients are typically diagnosed when the disease progresses to a more advanced stage. The objective of this contribution is to predict Alzheimer’s early stages, not only dementia itself. To carry out this objective, different types of SVM and CNN machine learning classifiers will be used, as well as two different feature selection algorithms: PCA and mRMR. The different experiments and their performance are compared when classifying patients from MRI images. The newness of the experiments conducted in this research includes the wide range of stages that we aim to predict, the processing of all the available information simultaneously and the Segmentation routine implemented in SPM12 for preprocessing. We will make use of multiple slices and consider different parts of the brain to give a more accurate response. Overall, excellent results have been obtained, reaching a maximum F1 score of 0.9979 from the SVM and PCA classifier. Full article

Electronic health records (EHRs) can be very difficult to analyze since they usually contain many missing values. To build an efficient predictive model, a complete dataset is necessary. An EHR usually contains high-dimensional longitudinal time series data. Most commonly used imputation methods do not consider the importance of temporal information embedded in EHR data. Besides, most time-dependent neural networks such as recurrent neural networks (RNNs) inherently consider the time steps to be equal, which in many cases, is not appropriate. This study presents a method using the gated recurrent unit (GRU), neural ordinary differential equations (ODEs), and Bayesian estimation to incorporate the temporal information and impute sporadically observed time series measurements in high-dimensional EHR data. Full article

Metagenomics promises to provide new valuable insights into the role of microbiomes in eukaryotic hosts such as humans. Due to the decreasing costs for sequencing, public and private repositories for human metagenomic datasets are growing fast. Metagenomic datasets can contain terabytes of raw data, which is a challenge for data processing but also an opportunity for advanced machine learning methods like deep learning that require large datasets. However, in contrast to classical machine learning algorithms, the use of deep learning in metagenomics is still an exception. Regardless of the algorithms used, they are usually not applied to raw data but require several preprocessing steps. Performing this preprocessing and the actual analysis in an automated, reproducible, and scalable way is another challenge. This and other challenges can be addressed by adjusting known big data methods and architectures to the needs of microbiome analysis and DNA sequence processing. A conceptual architecture for the use of machine learning and big data on metagenomic data sets was recently presented and initially validated to analyze the rumen microbiome. The same architecture can be used for clinical purposes as is discussed in this paper. Full article

A whole-body physiology model of inflammatory burn injury was used to train an algorithm to correctly detect patients’ states. The physiology model of a thermal injury takes the surface area of patient skin burned as an input to the model and responds to common treatments. This model is leveraged to build a database of patient physiology as a function of total body surface area burn, without treatment, over a 48-h window. Using this database, we train a model to determine patient injury status as a function of the available physiology data. The algorithm can group virtual patients into three distinct categories, corresponding to long term patient health. The results show that, given an initial virtual patient and injury, the algorithm can correctly determine the placement of that patient into the corresponding category, effectively classifying long term patient outcomes. Full article

Sleep deficiency impacts the quality of life and may have serious health consequences in the long run. Questionnaire-based subjective assessment of sleep deficiency has many limitations. On the other hand, objective assessment of sleep deficiency is challenging. In this study, we propose a polysomnography-based mathematical model for computing baseline sleep deficiency severity score and then investigated the estimation of sleep deficiency severity using features available only from wearable sensor data including heart rate variability and single-channel electroencephalography for a dataset of 500 subjects. We used Monte-Carlo feature selection (MCFS) and inter-dependency discovery for selecting the best features and removing multi-collinearity. For developing the Regression model we investigated both the frequentist and the Bayesian approaches. An artificial neural network achieved the best performance of RMSE = 5.47 and an R-squared value of 0.67 for sleep deficiency severity estimation. The developed method is comparable to conventional methods of Functional Outcome of Sleep Questionnaire and Epworth Sleepiness Scale for assessing the impact of sleep apnea on sleep deficiency. Moreover, the results pave the way for reliable and interpretable sleep deficiency severity estimation using single-channel EEG. Full article

Today Deep Learning (DL) is state-of-the-art in medical imaging segmentation tasks, including accurate localization of abdominal organs in MRI images. But segmentation still exhibits inaccuracies, which may be due to texture similarities, proximity or confusion between organs, morphology variations, acquisition conditions or other parameters. Examples include regions classified as the wrong organ, some noisy regions and inaccuracies near borders. To improve robustness, the DL output can be supplemented by more traditional image postprocessing operations that enforce simple semantic invariants. In this paper we define and apply totally automatic post-processing operations applying semantic invariants to correct segmentation mistakes. Organs are assigned relative spatial location restrictions (atlas fencing), 3D organ continuity requirements (envelop continuity), and smoothness constraints. A reclassification is done within organ envelopes to correct classification mistakes, and noise is removed (fencing, enveloping, noise removal, re-classifying and smoothing). Our experimental evaluation quantifies the improvement and compares the resulting quality with prior work on DL-based organ segmentation. Based on the experiments, we conclude post-processing improved the Jaccard index over independent test MRI sequences by a sum of 12 to 25 percentage points over the four segmented organs. This work has an important impact on research and practical application of DL because it describes how to post-process, quantifies the advantages, and can be applied to any DL approach. Full article

Background: Multiple myeloma (MM) is one of the most common cancers of the blood system. N6-methyladenosine (m6A) plays an important role in cancer progression. We aimed to investigate the prognostic relevance of the m6A score in multiple myeloma through a series of bioinformatics analyses. Methods: The microarray dataset GSE4581 and GSE57317 used in this study were downloaded from the Gene Expression Omnibus (GEO) database. The m6A score was calculated using the GSVA package. The Random forests, univariate Cox regression analysis and Lasso analyses were performed for the differentially expressed genes (DEGs). Kaplan–Meier analysis and an ROC curve were used to diagnose the effectiveness of the model. Results: The GSVA R software package was used to predict the function. A total of 21 m6A genes were obtained, and 286 DEGs were identified between high and low m6A score groups. The risk model was constructed and composed of PRX, LBR, RB1, FBXL19-AS1, ARSK, MFAP3L, SLC44A3, UNC119 and SHCBP1. Functional analysis of risk score showed that with the increase in the risk score, Activated CD4 T cells, Memory B cells and Type 2 T helper cells were highly infiltrated. Conclusions: Immune checkpoints such as HMGB1, TGFB1, CXCL9 and HAVCR2 were significantly positively correlated with the risk score. We believe that the m6A score has a certain prognostic value in multiple myeloma. Full article