Leaders in Pharmaceutical Business Intelligence (LPBI) Group

⁦@Celgene⁩ CC-220 binds to proteins degraded exposure correlates with B cell depletion normal T cells SLE IS THE NEW INDICATION of a repurpose of thalidomide and another drug for melanoma GENETIC DOSE-response portal: genetics, interrogation pleiotropy data analysis visual

Dr. Pledge ⁦@Celgene⁩ #GenMed2019 @pharma_BI @AVIVA1950 human genetics and drug discovery drug R&D attrition drug value to patient in decline failure in Phase 2&3 lack of efficacy cause hi drug price human as the model organism longitudinal test therapeutics on human phyno

⁦@GSK⁩ #GenMed2019 @pharma_BI @AVIVA1950 from genetics to target selection finding genetic evidence new opportunities cross-biobank research other RWD genetic data enabler: biobanks FINGEN (Finland collaboration) 23andme GWAS case control prevention disease trajectories

#GenMed2019 @pharma_BI @AVIVA1950 Dr. Rader UPenn Gain of function mutation increase HDL-C therapeutic relevance LCAT Fig below is on TRL

Dr. Rader UPenn Abeta- lipoproteinemia reduce LDL in serum-secretion increase lipid in liver Lomitspide Mipomersen rare Mendelian disorders yielded targets common diseases triglyceride-rich Lipoff protein TG LIPASE critical regulator of ApoC-III ANGPTL3 ANGPTL4 human knockouts

#GenMed2019 @pharma_BI @AVIVA1950 CRISPR tool to perturb enhancers REGULATORY elements by oligo pool pool of gRNA ScanDel pooled deletion screen HPRT1 Utica acid metabolism &CNS function scan deletions across the HPRT1 locus long deletion between two CRISPR cuts one deletion

#GenMed2019 @pharma_BI @AVIVA1950 Dr. Gupta ⁦@broadinstitute⁩ ⁦@MGH_RI⁩ 6p24 SNP coronary disease Justine acetylation vascular tissue variant in stem-cells differentiation into vascular endothelial cells or vascular muscle cells CRISPR/Cas9 heterozygous deletion

#GenMed2019 @pharma_BI @AVIVA1950 chromatin modifiers in De novo mutation related to CVD

#GenMed2019 @pharma_BI @AVIVA1950 Adrenal gland behave like tumor antibiotics as therapeutic to rare mutation K NaCl in Kidney

#GenMed2019 @pharma_BI @AVIVA2950 Common variants small effect on polygenic risk score purifying selection heterozygous mutation dominant lethals caused by mutations Sequence outside coding regions utility coding than non-coding variants SEQ EXOME 20,000 genes 1% genome SLC26A3

#GenMed2019 @pharma_BI @AVIVA1950 Prof. Lifting, Rockefeller University alleles genotype and phenotype links HTN cause death single mutation how kidney handle salt: extreme BP modulate loci to normalize BP Strategy to lower salt to control BP FDA identify genes vs biological

#GenMed2019 @pharma_BI @AVIVA1950 Immune Infiltration Hashimoto Crohn’s RNA-Seq 73 infiltration phenotypes amount of cell types tissue-specific genetics CUX1 gene expression neutrophils in Lungs

#GenMed2019 @pharma_BI @AVIVA1950 Immune-diseases GWAS Variants Treg role in homeostasis on immune system affect 10% of European Population RA, biological vs small molecules risk allele gene expression

#GenMed2019 @pharma_BI @AVIVA1950 Population with high risks for BRCA1 or 2 #TTR 1 in 30 Rick in African American carriers BRCA1or2 60% no cancer occurs ⁦@MountSinaiNYC⁩

#GenMed2019 @pharma_BI @AVIVA1950 Allele-specific reporter assays C G luciferase Multiple regulatory risk allele CRISPR/Cas9 genome editing allele vs Epigene Editing point mutation synthetic transcription factor covalent histone enhancer activation via dCas9-P300 10-6 kB away

#GenMed2019 @pharma_BI @AVIVA1950 Hyperglycemia during pregnancy adverse pregnancies outcome genetic variation on Chromosome 10 1st intron of HKDC1 epigenetic signals of gene regulation

#GenMed2019 @pharma_BI @AVIVA1950 GWAS vs gene regulation non coding regions variant perturbed gene expression target gene identification difficult <50 % enhancers target their nearest gene linkage disequilibrium sensitivity of system perturbation of gene casual gene function Epi

#GenMed2019 @pharma_BI @AVIVA1950 Full picture #genetics , longitudinal vs cross section interventions, genetics to predict obesity by Test vs Disease susceptibility of newborn babies top 5% vs 20% for clinical sensitivity specificity 0.8 #family history BETTER predictor S/S 0.5