Familial adenomatous polyposis (FAP) is a genetic disease causing hundreds of premalignant polyps in affected persons and is an ideal model to study transitions of early precancer states to colorectal cancer (CRC). We performed deep multiomic profiling of 93 samples, including normal mucosa, benign polyps and dysplastic polyps, from six persons with FAP. Transcriptomic, proteomic, metabolomic and lipidomic analyses revealed a dynamic choreography of thousands of molecular and cellular events that occur during precancerous transitions toward cancer formation.
View Article and Find Full Text PDFBackground: Metastatic progress is the primary cause of death in most cancers, yet the regulatory dynamics driving the cellular changes necessary for metastasis remain poorly understood. Multi-omics approaches hold great promise for addressing this challenge; however, current analysis tools have limited capabilities to systematically integrate transcriptomic, epigenomic, and cistromic information to accurately define the regulatory networks critical for metastasis.
Results: To address this limitation, we use a purposefully generated cellular model of colon cancer invasiveness to generate multi-omics data, including expression, accessibility, and selected histone modification profiles, for increasing levels of invasiveness.
Background: Identification of functional non-coding variants and their mechanistic interpretation is a major challenge of modern genomics, especially for precision medicine. Transcription factor (TF) binding profiles and epigenomic landscapes in reference samples allow functional annotation of the genome, but do not provide ready answers regarding the effects of non-coding variants on phenotypes. A promising computational approach is to build models that predict TF-DNA binding from sequence, and use such models to score a variant's impact on TF binding strength.
View Article and Find Full Text PDFRecent studies have analyzed large-scale data sets of gene expression to identify genes associated with interindividual variation in phenotypes ranging from cancer subtypes to drug sensitivity, promising new avenues of research in personalized medicine. However, gene expression data alone is limited in its ability to reveal -regulatory mechanisms underlying phenotypic differences. In this study, we develop a new probabilistic model, called pGENMi, that integrates multi-omic data to investigate the transcriptional regulatory mechanisms underlying interindividual variation of a specific phenotype-that of cell line response to cytotoxic treatment.
View Article and Find Full Text PDFThe discordance between genome size and the complexity of eukaryotes can partly be attributed to differences in repeat density. The Muller F element (∼5.2 Mb) is the smallest chromosome in , but it is substantially larger (>18.
View Article and Find Full Text PDFChanges in gene regulatory networks (GRNs) underlie the evolution of morphological novelty and developmental system drift. The fruitfly Drosophila melanogaster and the dengue and Zika vector mosquito Aedes aegypti have substantially similar nervous system morphology. Nevertheless, they show significant divergence in a set of genes co-expressed in the midline of the Drosophila central nervous system, including the master regulator single minded and downstream genes including short gastrulation, Star, and NetrinA.
View Article and Find Full Text PDFThe Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D.
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