Quantitative Biology

Proteins execute various activities required by biological cells. Further, they structurally support and pro-mote important biochemical reactions which functionally are sparked by active-sites. Active-sites are regions where reac-tions and binding events take place directly; they foster pro-tein purpose. Describing functional relationships depends on factors that incorporate sequence, structure, and the biochem-ical properties of amino acids that form proteins. Our ap-proach to active-site description is computational, and many other approaches utilizing available protein data fall short of ideal. Successful recognition of functional interactions is cru-cial to advancements in protein annotation and the bioinfor-matics field at large. This research outlines our Multiple Structure Torsion Angle Alignment (msTALI) as a suitable strategy for addressing active-site identification by comparing results to other existing methods. Specifically, we address the precision of msTALI across three protein families. Our target proteins are PDBIDs 1A2B, 1B4V, 1B8S, 1COY, 1CXZ, 3COX, 1D7E, 1DPF, 1F9I, 1FTN, 1IJH, 1KOU, 1NWZ, 2PHY, and 1SIC.

As the world ages, elderly care becomes a big concern of the society. To address the elderly's issues on dementia and fall risk, we have investigated smart cognitive and fall risk assessment with machine learning methodology based on the data collected from finger tapping test and Timed Up and Go (TUG) test. Meanwhile, we have discovered the associations between cognition and finger motion from finger tapping data and the association between fall risk and gait characteristics from TUG data. In this paper, we jointly analyze the finger tapping and gait characteristics data with copula entropy. We find that the associations between certain finger tapping characteristics ('number of taps', 'average interval of tapping', 'frequency of tapping' of both hands of bimanual inphase and those of left hand of bimanual untiphase) and TUG score are relatively high. According to this finding, we propose to utilize this associations to improve the predictive models of automatic fall risk assessment we developed previously. Experimental results show that using the characteristics of both finger tapping and gait as inputs of the predictive models of predicting TUG score can considerably improve the prediction performance in terms of MAE compared with using only one type of characteristics.

Background: Drug-drug interactions (DDIs) refer to processes triggered by the administration of two or more drugs leading to side effects beyond those observed when drugs are administered by themselves. Due to the massive number of possible drug pairs, it is nearly impossible to experimentally test all combinations and discover previously unobserved side effects. Therefore, machine learning based methods are being used to address this issue. Methods: We propose a Siamese self-attention multi-modal neural network for DDI prediction that integrates multiple drug similarity measures that have been derived from a comparison of drug characteristics including drug targets, pathways and gene expression profiles. Results: Our proposed DDI prediction model provides multiple advantages: 1) It is trained end-to-end, overcoming limitations of models composed of multiple separate steps, 2) it offers model explainability via an Attention mechanism for identifying salient input features and 3) it achieves similar or better prediction performance (AUPR scores ranging from 0.77 to 0.92) compared to state-of-the-art DDI models when tested on various benchmark datasets. Novel DDI predictions are further validated using independent data resources. Conclusions: We find that a Siamese multi-modal neural network is able to accurately predict DDIs and that an Attention mechanism, typically used in the Natural Language Processing domain, can be beneficially applied to aid in DDI model explainability.

Many ecological and spatial processes are complex in nature and are not accurately modeled by linear models. Regression trees promise to handle the high-order interactions that are present in ecological and spatial datasets, but fail to produce physically realistic characterizations of the underlying landscape. The "autocart" (autocorrelated regression trees) R package extends the functionality of previously proposed spatial regression tree methods through a spatially aware splitting function and novel adaptive inverse distance weighting method in each terminal node. The efficacy of these autocart models, including an autocart extension of random forest, is demonstrated on multiple datasets. This highlights the ability of autocart to model complex interactions between spatial variables while still providing physically realistic representations of the landscape.

Sleep has been shown to be an indispensable and important component of patients recovery process. Nonetheless, sleep quality of patients in the Intensive Care Unit (ICU) is often low, due to factors such as noise, pain, and frequent nursing care activities. Frequent sleep disruptions by the medical staff and/or visitors at certain times might lead to disruption of patient sleep-wake cycle and can also impact the severity of pain. Examining the association between sleep quality and frequent visitation has been difficult, due to lack of automated methods for visitation detection. In this study, we recruited 38 patients to automatically assess visitation frequency from captured video frames. We used the DensePose R-CNN (ResNet-101) model to calculate the number of people in the room in a video frame. We examined when patients are interrupted the most, and we examined the association between frequent disruptions and patient outcomes on pain and length of stay.

Accurate segmentation of cerebral vasculature and a quantitative assessment of cerebrovascular morphology is critical to various diagnostic and therapeutic purposes and is pertinent to studying brain health and disease. However, this is still a challenging task due to the complexity of the vascular imaging data. We propose an automated method for cerebral vascular segmentation without the need of any manual intervention as well as a method to skeletonize the binary volume to extract vascular geometric features which can characterize vessel structure. We combine a probabilistic vessel-enhancing filtering with an active-contour technique to segment magnetic resonance and computed tomography angiograms (MRA and CTA) and subsequently extract the vessel centerlines and diameters to calculate the geometrical properties of the vasculature. Our method was validated using a 3D phantom of the Circle-of-Willis region with 84% mean Dice Similarity and 85% mean Pearson Correlation with minimal modified Hausdorff distance error. We applied this method to a dataset of healthy subjects and stroke patients and present a quantitative comparison between them. We found significant differences in the geometric features including total length (2.88 +/- 0.38 m for healthy and 2.20 +/- 0.67 m for stroke), volume (40.18 +/- 25.55 ml for healthy and 34.43 +/- 21.83 ml for stroke), tortuosity (3.24 +/- 0.88 rad/cm for healthy and 5.80 +/- 0.92 rad/cm for stroke) and fractality (box dimension 1.36 +/- 0.28 for healthy vs. 1.69 +/- 0.20 for stroke). This technique can be applied on any imaging modality and can be used in the future to automatically obtain the 3D segmented vasculature for diagnosis and treatment planning of Stroke and other cerebrovascular diseases (CVD) in the clinic and also to study the morphological changes caused by various CVD.

Recording muscle tendon junction displacements during movement, allows separate investigation of the muscle and tendon behaviour, respectively. In order to provide a fully-automatic tracking method, we employ a novel deep learning approach to detect the position of the muscle tendon junction in ultrasound images. We utilize the attention mechanism to enable the network to focus on relevant regions and to obtain a better interpretation of the results. Our data set consists of a large cohort of 79 healthy subjects and 28 subjects with movement limitations performing passive full range of motion and maximum contraction movements. Our trained network shows robust detection of the muscle tendon junction on a diverse data set of varying quality with a mean absolute error of 2.55 ± 1 mm. We show that our approach can be applied for various subjects and can be operated in real-time. The complete software package is available for open-source use via: this https URL

INTRODUCTION: Heterogeneity in the progression of Alzheimer's disease makes it challenging to predict the rate of cognitive and functional decline for individual patients. Tools for short-term prediction could help enrich clinical trial designs and focus prevention strategies on the most at-risk patients. METHOD: We built a prognostic model using baseline cognitive scores and MRI-based features to determine which subjects with mild cognitive impairment remained stable and which functionally declined (measured by a two-point increase in CDR-SB) over 2 and 3-year follow-up periods, periods typical of the length of clinical trials. RESULTS: Combining both sets of features yields 77% accuracy (81% sensitivity and 75% specificity) to predict cognitive decline at 2 years (74% accuracy at 3 years with 75% sensitivity and 73% specificity). Using this tool to select trial participants yields a 3.8-fold decrease in the required sample size for a 2-year study (2.8-fold decrease for a 3-year study) for a hypothesized 25% treatment effect to reduce cognitive decline. DISCUSSION: This cohort enrichment tool could accelerate treatment development by increasing power in clinical trials.

Visual categorization and learning of visual categories exhibit early onset, however the underlying mechanisms of early categorization are not well understood. The main limiting factor for examining these mechanisms is the limited duration of infant cooperation (10-15 minutes), which leaves little room for multiple test trials. With its tight link to visual attention, eye tracking is a promising method for getting access to the mechanisms of category learning. But how should researchers decide which aspects of the rich eye tracking data to focus on? To date, eye tracking variables are generally handpicked, which may lead to biases in the eye tracking data. Here, we propose an automated method for selecting eye tracking variables based on analyses of their usefulness to discriminate learners from non-learners of visual categories. We presented infants and adults with a category learning task and tracked their eye movements. We then extracted an over-complete set of eye tracking variables encompassing durations, probabilities, latencies, and the order of fixations and saccadic eye movements. We compared three statistical techniques for identifying those variables among this large set that are useful for discriminating learners form non-learners: ANOVA ranking, Bayes ranking, and L1 regularized logistic regression. We found remarkable agreement between these methods in identifying a small set of discriminant variables. Moreover, the same eye tracking variables allow us to classify category learners from non-learners among adults and 6- to 8-month-old infants with accuracies above 71%.

While there are many different methods for peak detection, no automatic methods for marking peak boundaries to calculate area under the curve (AUC) and signal-to-noise ratio (SNR) estimation exist. An algorithm for the automation of liquid chromatography tandem mass spectrometry (LC-MS/MS) mass chromatogram quantification was developed and validated. Continuous wavelet transformation and other digital signal processing methods were used in a multi-step procedure to calculate concentrations of six different analytes. To evaluate the performance of the algorithm, the results of the manual quantification of 446 hair samples with 6 different steroid hormones by two experts were compared to the algorithm results. The proposed approach of automating mass chromatogram quantification is reliable and valid. The algorithm returns less nondetectables than human raters. Based on signal to noise ratio, human non-detectables could be correctly classified with a diagnostic performance of AUC = 0.95. The algorithm presented here allows fast, automated, reliable, and valid computational peak detection and quantification in LC- MS/MS.