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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
Enrichment and aggregation of topological motifs are independent organizational principles of integrated interaction networks
Topological network motifs represent functional relationships within and
between regulatory and protein-protein interaction networks. Enriched motifs
often aggregate into self-contained units forming functional modules.
Theoretical models for network evolution by duplication-divergence mechanisms
and for network topology by hierarchical scale-free networks have suggested a
one-to-one relation between network motif enrichment and aggregation, but this
relation has never been tested quantitatively in real biological interaction
networks. Here we introduce a novel method for assessing the statistical
significance of network motif aggregation and for identifying clusters of
overlapping network motifs. Using an integrated network of transcriptional,
posttranslational and protein-protein interactions in yeast we show that
network motif aggregation reflects a local modularity property which is
independent of network motif enrichment. In particular our method identified
novel functional network themes for a set of motifs which are not enriched yet
aggregate significantly and challenges the conventional view that network motif
enrichment is the most basic organizational principle of complex networks.Comment: 12 pages, 5 figure
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