17,906 research outputs found
Machine Learning and Integrative Analysis of Biomedical Big Data.
Recent developments in high-throughput technologies have accelerated the accumulation of massive amounts of omics data from multiple sources: genome, epigenome, transcriptome, proteome, metabolome, etc. Traditionally, data from each source (e.g., genome) is analyzed in isolation using statistical and machine learning (ML) methods. Integrative analysis of multi-omics and clinical data is key to new biomedical discoveries and advancements in precision medicine. However, data integration poses new computational challenges as well as exacerbates the ones associated with single-omics studies. Specialized computational approaches are required to effectively and efficiently perform integrative analysis of biomedical data acquired from diverse modalities. In this review, we discuss state-of-the-art ML-based approaches for tackling five specific computational challenges associated with integrative analysis: curse of dimensionality, data heterogeneity, missing data, class imbalance and scalability issues
Reciprocal Perspective for Improved Protein-Protein Interaction Prediction
All protein-protein interaction (PPI) predictors require the determination of an operational decision threshold when differentiating positive PPIs from negatives. Historically, a single global threshold, typically optimized via cross-validation testing, is applied to all protein pairs. However, we here use data visualization techniques to show that no single decision threshold is suitable for all protein pairs, given the inherent diversity of protein interaction profiles. The recent development of high throughput PPI predictors has enabled the comprehensive scoring of all possible protein-protein pairs. This, in turn, has given rise to context, enabling us now to evaluate a PPI within the context of all possible predictions. Leveraging this context, we introduce a novel modeling framework called Reciprocal Perspective (RP), which estimates a localized threshold on a per-protein basis using several rank order metrics. By considering a putative PPI from the perspective of each of the proteins within the pair, RP rescores the predicted PPI and applies a cascaded Random Forest classifier leading to improvements in recall and precision. We here validate RP using two state-of-the-art PPI predictors, the Protein-protein Interaction Prediction Engine and the Scoring PRotein INTeractions methods, over five organisms: Homo sapiens, Saccharomyces cerevisiae, Arabidopsis thaliana, Caenorhabditis elegans, and Mus musculus. Results demonstrate the application of a post hoc RP rescoring layer significantly improves classification (p < 0.001) in all cases over all organisms and this new rescoring approach can apply to any PPI prediction method
Herb Target Prediction Based on Representation Learning of Symptom related Heterogeneous Network.
Traditional Chinese Medicine (TCM) has received increasing attention as a complementary approach or alternative to modern medicine. However, experimental methods for identifying novel targets of TCM herbs heavily relied on the current available herb-compound-target relationships. In this work, we present an Herb-Target Interaction Network (HTINet) approach, a novel network integration pipeline for herb-target prediction mainly relying on the symptom related associations. HTINet focuses on capturing the low-dimensional feature vectors for both herbs and proteins by network embedding, which incorporate the topological properties of nodes across multi-layered heterogeneous network, and then performs supervised learning based on these low-dimensional feature representations. HTINet obtains performance improvement over a well-established random walk based herb-target prediction method. Furthermore, we have manually validated several predicted herb-target interactions from independent literatures. These results indicate that HTINet can be used to integrate heterogeneous information to predict novel herb-target interactions
Mean-Field Theory of Meta-Learning
We discuss here the mean-field theory for a cellular automata model of
meta-learning. The meta-learning is the process of combining outcomes of
individual learning procedures in order to determine the final decision with
higher accuracy than any single learning method. Our method is constructed from
an ensemble of interacting, learning agents, that acquire and process incoming
information using various types, or different versions of machine learning
algorithms. The abstract learning space, where all agents are located, is
constructed here using a fully connected model that couples all agents with
random strength values. The cellular automata network simulates the higher
level integration of information acquired from the independent learning trials.
The final classification of incoming input data is therefore defined as the
stationary state of the meta-learning system using simple majority rule, yet
the minority clusters that share opposite classification outcome can be
observed in the system. Therefore, the probability of selecting proper class
for a given input data, can be estimated even without the prior knowledge of
its affiliation. The fuzzy logic can be easily introduced into the system, even
if learning agents are build from simple binary classification machine learning
algorithms by calculating the percentage of agreeing agents.Comment: 23 page
Classifying pairs with trees for supervised biological network inference
Networks are ubiquitous in biology and computational approaches have been
largely investigated for their inference. In particular, supervised machine
learning methods can be used to complete a partially known network by
integrating various measurements. Two main supervised frameworks have been
proposed: the local approach, which trains a separate model for each network
node, and the global approach, which trains a single model over pairs of nodes.
Here, we systematically investigate, theoretically and empirically, the
exploitation of tree-based ensemble methods in the context of these two
approaches for biological network inference. We first formalize the problem of
network inference as classification of pairs, unifying in the process
homogeneous and bipartite graphs and discussing two main sampling schemes. We
then present the global and the local approaches, extending the later for the
prediction of interactions between two unseen network nodes, and discuss their
specializations to tree-based ensemble methods, highlighting their
interpretability and drawing links with clustering techniques. Extensive
computational experiments are carried out with these methods on various
biological networks that clearly highlight that these methods are competitive
with existing methods.Comment: 22 page
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