1. High-throughput data used in bioinformatics
physical distance between enhancers and their target gene promoters (which could be upto 1 Mb apart)
genome compartmentization
location specific effect on expression
DNA methylation
histone modification
mutations
gene duplication
genome rearrangement
essential biological processes
gene regulation networks
phylogenomic relationships
High-throughput data used in bioinformatics
Epigenetic
Genomic
Whole exome sequencing
Transcripto-mic
Ribosome profiling
Proteomic
Protein and RNA Structure
Cistromic
Genome architecture
somatic mutations in coding regions
alternatively spliced isoforms
Fig. ? Major types of high-throughput data and their key information relevant to drug discovery.
genome-wise binding sites of proteins (e.g., transcription factors)
differential gene regulation
somatic mutation
alternative splicing
different transcription start and termination sites
binding and docking properties
location of charged residues for electrostatic interactions
enzyme-substrate and ligand-protein interactions
translation regulation
translation mechanisms (e.g., cap-dependent or internal ribosomal entry)
differential translation initiation, elongation and termination
translation rate of individual proteins
differential protein abundance
posttranslational modification
signal peptide and cellular localization

2. Applications of data Molecular biology Molecular evolution
Molecular phylogenetics
Molecular ecology
Developmental biology
Biomedical sciences
Biopharmaceutical sciences
Genetics/epigenetics ……

3. Recruiting methyl-CpG binding proteins
Negatively charged DNA backbone wrapping tightly around histone
CpG DNA methylation
LM: bisulfite sequencing
BQ: what is the methylation signal? Why some CpG methylated and some not? Flanking signal or trans-acting factors or both?
Gene on/off
Recruiting deacetylase to restore positive charge to histone
(hypothetical) negatively charged epigenetic writer, reader or eraser
DNA/protein binding mediated by DNA methylation, methy-CpG binding proteins, acetylation/deacetylation, and electrostatic interaction
LM: ChIP-on-chip, ChIP-Seq
BQ: What are the signals on protein binding sites at sequence and structural level? What is the spatial (tissue- or cell-specific) and temporal (developmental) pattern of protein/DNA binding? What is the effect of changed electric charge of histone through acetylation/deacetylation affect electrostatic interaction with other DNA-binding proteins
Fig. ? A general framework of epigenetic effects on gene expression, through 1) DNA methylation and histone acetylation/deacetylation, 2) alteration of DNA-binding proteins and consequent protein-DNA and protein-protein interactions, and 3) alteration of long-distance interactions such as enhancer-promotor interactions. LM – laboratory method, BQ: sample bioinformatic questions. - +
Histone deacetylated
DNA
Alteration of long-distance interaction patterns changes genome architecture (e.g., enhancers and promoters far apart along the genome are brought together)
LM: Hi-C
BQ: How much variation in gene expression can be explained by its physical location? What genes tend to be spatially associated? What genes tend to change its physical location in response to intra- and extracellular environment?
DNA
enhancer
Protein complex bringing the two together
promoter