ACM-BCB ... ... : the ... ACM Conference on Bioinformatics, Computational Biology and Biomedicine. ACM Conference on Bioinformatics, Computational Biology and Biomedicine最新文献

Alternative splicing significantly contributes to proteomic diversity and mis-regulation of splicing can cause diseases in human. Although both genomic and chromatin features have been shown to associate with splicing, the mechanisms by which various chromatin marks influence splicing is not clear for the most part. Moreover, it is not known whether the influence of specific genomic features on splicing is potentially modulated by the chromatin context. Here we report a deep neural network (DNN) model for predicting exon inclusion based on comprehensive genomic and chromatin features. Our analysis in three cell lines shows that, while both genomic and chromatin features can predict splicing to varying degrees, genomic features are the primary drivers of splicing, and the predictive power of chromatin features can largely be explained by their correlation with genomic features; chromatin features do not yield substantial independent contribution to splicing predictability. However, our model identified specific interactions between chromatin and genomic features suggesting that the effect of genomic elements may be modulated by chromatin context.

Clinicians in intensive care units (ICUs) rely on standardized scores as risk prediction models to predict a patient's vulnerability to life-threatening events. Conventional Current scales calculate scores from a fixed set of conditions collected within a specific time window. However, modern monitoring technologies generate complex, temporal, and multimodal patient data that conventional prediction models scales cannot fully utilize. Thus, a more sophisticated model is needed to tailor individual characteristics and incorporate multiple temporal modalities for a personalized risk prediction. Furthermore, most scales models focus on adult patients. To address this needdeficiency, we propose a newly designed ICU risk prediction system, called icuARM-II, using a large-scaled pediatric ICU database from Children's Healthcare of Atlanta. This novel database contains clinical data collected in 5,739 ICU visits from 4,975 patients. We propose a temporal association rule mining framework giving clinicians a potential to perform predict risks prediction based on all available patient conditions without being restricted by a fixed observation window. We also develop a new metric that can rigidly assesses the reliability of all all generated association rules. In addition, the icuARM-II features an interactive user interface. Using the icuARM-II, our results demonstrated showed a use case of short-term mortality prediction using lab testing results, which demonstrated a potential new solution for reliable ICU risk prediction using personalized clinical data in a previously neglected population.

Robust prediction models are important for numerous science, engineering, and biomedical applications. However, best-practice procedures for optimizing prediction models can be computationally complex, especially when choosing models from among hundreds or thousands of parameter choices. Computational complexity has further increased with the growth of data in these fields, concurrent with the era of "Big Data". Grid computing is a potential solution to the computational challenges of Big Data. Desktop grid computing, which uses idle CPU cycles of commodity desktop machines, coupled with commercial cloud computing resources can enable research labs to gain easier and more cost effective access to vast computing resources. We have developed omniClassifier, a multi-purpose prediction modeling application that provides researchers with a tool for conducting machine learning research within the guidelines of recommended best-practices. omniClassifier is implemented as a desktop grid computing system using the Berkeley Open Infrastructure for Network Computing (BOINC) middleware. In addition to describing implementation details, we use various gene expression datasets to demonstrate the potential scalability of omniClassifier for efficient and robust Big Data prediction modeling. A prototype of omniClassifier can be accessed at http://omniclassifier.bme.gatech.edu/.

Stress can lead to headaches and fatigue, precipitate addictive behaviors (e.g., smoking, alcohol and drug use), and lead to cardiovascular diseases and cancer. Continuous assessment of stress from sensors can be used for timely delivery of a variety of interventions to reduce or avoid stress. We investigate the feasibility of continuous stress measurement via two field studies using wireless physiological sensors - a four-week study with illicit drug users (n = 40), and a one-week study with daily smokers and social drinkers (n = 30). We find that 11+ hours/day of usable data can be obtained in a 4-week study. Significant learning effect is observed after the first week and data yield is seen to be increasing over time even in the fourth week. We propose a framework to analyze sensor data yield and find that losses in wireless channel is negligible; the main hurdle in further improving data yield is the attachment constraint. We show the feasibility of measuring stress minutes preceding events of interest and observe the sensor-derived stress to be rising prior to self-reported stress and smoking events.

Many text-mining studies have focused on the issue of named entity recognition and normalization, especially in the field of biomedical natural language processing. However, entity recognition is a complicated and difficult task in biomedical text. One particular challenge is to identify and resolve composite named entities, where a single span refers to more than one concept(e.g., BRCA1/2). Most bioconcept recognition and normalization studies have either ignored this issue, used simple ad-hoc rules, or only handled coordination ellipsis, which is only one of the many types of composite mentions studied in this work. No systematic methods for simplifying composite mentions have been previously reported, making a robust approach greatly needed. To this end, we propose a hybrid approach by integrating a machine learning model with a pattern identification strategy to identify the antecedent and conjuncts regions of a concept mention, and then reassemble the composite mention using those identified regions. Our method, which we have named SimConcept, is the first method to systematically handle most types of composite mentions. Our method achieves high performance in identifying and resolving composite mentions for three fundamental biological entities: genes (89.29% in F-measure), diseases (85.52% in F-measure) and chemicals (84.04% in F-measure). Furthermore, our results show that, using our SimConcept method can subsequently help improve the performance of gene and disease concept recognition and normalization.

The dynamic temporal regulatory effects of microRNA are not well known. We introduce a technique for integrating miRNA and mRNA time series microarray data with known disease pathology. The integrated analysis includes identifying both mRNA and miRNA that are signi cantly similar to the quantitative pathology. Potential regulatory miRNA/mRNA target pairs are identi ed through databases of both predicted and validated pairs. Finally, potential target pairs are ltered by examining the second derivatives of the fold changes over time. Our system was used on genome-wide microarray expression data of mouse lungs (n = 160) following aspiration of multi-walled carbon nanotubes. This system shows promise of readily identifying miRNA for further study as potential biomarker use.

We propose a framework for studying visual morphological patterns across histopathological whole-slide images (WSIs). Image representation is an important component of computer-aided decision support systems for histopathological cancer diagnosis. Such systems extract hundreds of quantitative image features from digitized tissue biopsy slides and produce models for prediction. The performance of these models depends on the identification of informative features for selection of appropriate regions-of-interest (ROIs) from heterogeneous WSIs and for development of models. However, identification of informative features is hindered by the semantic gap between human interpretation of visual morphological patterns and quantitative image features. We address this challenge by using data mining and information visualization tools to study spatial patterns formed by features extracted from sub-sections of WSIs. Using ovarian serous cystadenocarcinoma (OvCa) WSIs provided by the cancer genome atlas (TCGA), we show that (1) individual and (2) multivariate image features correspond to biologically relevant ROIs, and (3) supervised image feature selection can map histopathology domain knowledge to quantitative image features.

Genome-wide association studies (GWAS) analyze genetic variation (SNPs) across the entire human genome, searching for SNPs that are associated with certain phenotypes, most often diseases, such as breast cancer. In GWAS, we seek a ranking of SNPs in terms of their relevance to the given phenotype. However, because certain SNPs are known to be highly correlated with one another across individuals, it can be beneficial to take into account these correlations when ranking. If a SNP appears associated with the phenotype, and we question whether this association is real, the extent to which its neighbors (correlated SNPs) also appear associated can be informative. Therefore, we propose CollectRank, a ranking approach which allows SNPs to reinforce one another via the correlation structure. CollectRank is loosely analogous to the well-known PageRank algorithm. We first evaluate CollectRank on synthetic data generated from a variety of genetic models under different settings. The numerical results suggest CollectRank can significantly outperform common GWAS methods at the cost of a small amount of extra computation. We further evaluate CollectRank on two real-world GWAS on breast cancer and atrial fibrillation/flutter, and CollectRank performs well in both studies. We finally provide a theoretical analysis that also suggests CollectRank's advantages.

Computational protein-protein docking is a valuable tool for determining the conformation of complexes formed by interacting proteins. Selecting near-native conformations from the large number of possible models generated by docking software presents a significant challenge in practice. We introduce a novel method for ranking docked conformations based on the degree of overlap between the interface residues of a docked conformation formed by a pair of proteins with the set of predicted interface residues between them. Our approach relies on a method, called PS-HomPPI, for reliably predicting protein-protein interface residues by taking into account information derived from both interacting proteins. PS-HomPPI infers the residues of a query protein that are likely to interact with a partner protein based on known interface residues of the homo-interologs of the query-partner protein pair, i.e., pairs of interacting proteins that are homologous to the query protein and partner protein. Our results on Docking Benchmark 3.0 show that the quality of the ranking of docked conformations using our method is consistently superior to that produced using ClusPro cluster-size-based and energy-based criteria for 61 out of the 64 docking complexes for which PS-HomPPI produces interface predictions. An implementation of our method for ranking docked models is freely available at: http://einstein.cs.iastate.edu/DockRank/.