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Kalen Robeson, Silvana Duran-Ortiz, Deb Walter, Katie Troike, Nate Sulecki Bioinformatics Journal Club 9-13-2016 Top Papers in Regulatory and Systems Genomics Gene Expression/Regulation: 1. Transcriptomics a. Analysis of genomic variation in non-coding elements using population-scale sequencing data from the 1000 Genomes Project b. Guilt by association is the exception rather than the rule in gene networks c. Systematic dissection of regulatory motifs in 2000 predicted human enhancers using a massively parallel reporter assay d. Promoter Sequence Determines the Relationship between Expression Level and Noise e. Predicting the sequence specificities of DNA- and RNA-binding proteins by deep learning f. Inferring interaction type in gene regulatory networks using co-expression data 2. Protein/DNA or Protein/Protein a. Accurate inference of transcription factor binding from DNA sequence and chromatin accessibility data b. Comprehensive genome-wide protein-DNA interactions detected at singlenucleotide resolution c. Discriminative prediction of mammalian enhancers from DNA sequence d. Dynamic exchange at regulatory elements during chromatin remodeling underlies assisted loading mechanism e. Mapping and analysis of chromatin state dynamics in nine human cell types f. DNaseI sensitivity QTLs are a major determinant of human expression variation g. An expansive human regulatory lexicon encoded in transcription factor footprints h. Linking the signaling cascades and dynamic regulatory networks controlling stress responses i. Genomic regions flanking E-box binding sites influence DNA binding specificity of bHLH transcription factors through DNA shape j. Probing DNA shape and methylation state on a genomic scale with DNase I k. Single-molecule dynamics of enhanceosome assembly in embryonic stem cells l. Determination and inference of eukaryotic transcription factor sequence specificity m. Coregulation of transcription factor binding and nucleosome occupancy through DNA features of mammalian enhancers n. TFBSshape: a motif database for DNA shape features of transcription factor binding sites o. Quantitative modeling of transcription factor binding specificities using DNA shape Expression in Cancer and Other Diseases: 1. An extensive microRNA-mediated network of RNA-RNA interactions regulates established oncogenic pathways in glioblastoma 2. Prioritizing candidate disease genes by network-based boosting of genome-wide association data 3. The human splicing code reveals new insights into the genetic determinants of disease 4. Integration of genomic data enables selective discovery of breast cancer drivers Statistics/Mathmatics: 1. A statistical framework for joint eQTL analysis in multiple tissues 2. Computational identification of diverse mechanisms underlying transcription factor-DNA occupancy 3. A community effort to assess and improve drug sensitivity prediction algorithms 4. Deconvolving the recognition of DNA shape from sequence 5. Elucidating Compound Mechanism of Action by Network Perturbation Analysis 6. A method to predict the impact of regulatory variants from DNA sequence Epigenetics: 1. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome 2. Large-scale imputation of epigenomic datasets for systematic annotation of diverse human tissues Expression During Development: 1. Comparison of D. melanogaster and C. elegans developmental stages, tissues, and cells by modENCODE RNA-seq data 2. Enhancer loops appear stable during development and are associated with paused polymerase 3. Genotype-environment interactions reveal causal pathways that mediate genetic effects on phenotype 4. Computational analysis of cell-to-cell heterogeneity in single-cell RNA-sequencing data reveals hidden subpopulations of cells 5. Joint annotation of chromatin state and chromatin conformation reveals relationships among domain types and identifies domains of cell type-specific expression Evolution: 1. A high-resolution map of human evolutionary constraint using 29 mammals 2. Cofactor binding evokes latent differences in DNA binding specificity between Hox proteins 3. Characterizing the genetic basis of transcriptome diversity through RNA-sequencing of 922 individuals