Identification, semantic annotation and comparison of combinations of functional elements in multiple biological conditions

Motivation: Approaches such as chromatin immunoprecipitation followed by sequencing (ChIP-seq) represent the standard for the identification of binding sites of DNA-associated proteins, including transcription factors and histone marks. Public repositories of omics data contain a huge number of experimental ChIP-seq data, but their reuse and integrative analysis across multiple conditions remain a daunting task. Results: We present the Combinatorial and Semantic Analysis of Functional Elements (CombSAFE), an efficient computational method able to integrate and take advantage of the valuable and numerous, but heterogeneous, ChIP-seq data publicly available in big data repositories. Leveraging natural language processing techniques, it integrates omics data samples with semantic annotations from selected biomedical ontologies; then, using hidden Markov models, it identifies combinations of static and dynamic functional elements throughout the genome for the corresponding samples. CombSAFE allows analyzing the whole genome, by clustering patterns of regions with similar functional elements and through enrichment analyses to discover ontological terms significantly associated with them. Moreover, it allows comparing functional states of a specific genomic region to analyze their different behavior throughout the various semantic annotations. Such findings can provide novel insights by identifying unexpected combinations of functional elements in different biological conditions.