1. Xiaole Shirley Liu STAT115, STAT215, BIO298, BIST520
Final Review
Xiaole Shirley Liu
STAT115, STAT215, BIO298, BIST520

2. Genomic techniques Gene expression profiling TF regulation: ChIP-seq
Expression Microarray and RNA-seq
TF regulation: ChIP-seq
Epigenetic profiling
Methylation array, BS-seq, ChIP-seq, DNase-seq, HiC
GWAS: SNP arrays
Genome sequencing: germline & somatic
High throughput screening
Genetic (si/shRNA, CRISPR screens) and chemical (drug screens)

3. Biological Problems
Transcriptional regulation and transcription factors
Epigenetics and chromatin factors
Human genetics and disease susceptibility
Cancer genomics and precision medicine

4. Binformatics Microarrays (RMA, LIMMA)
Ontology and pathway (DAVID, GSEA)
Batch removal (COMBAT, SVA)
NGS for DNA-seq (FastQC, BWA, STAR)
RNA-seq (DESeq, Kalisto, Sluth)
ChIP/DNase-seq (MACS, BETA)
GWAS (Plink, GCTA)
Genome-resequencing (GATK, Mutect)
Web resources: GEO, UCSC, CBioPortal

5. Statistics and Algorithms
R, BioConductor and python
Tukey bi-weight, median polish, qnorm, qq plot
Statistical test: t*-test, Chi-sq test, KS test, FDR adjustment
Hierarchical models, generalized linear models
K-means and hierarchical clustering
PCA, SVM
Burrows-Wheeler alignment
EM, Gibbs sampling
HMM, dynamics programming
LASSO and logistic regression
Survival analysis

6. CRISPR-Cas: Bacterial Adaptive Immune System
Clustered regularly interspaced short palindromic repeats

7. CRISPR/Cas9 Knockout
CRISPR guide RNA allows Cas9 to make ds breaks at specific genomic locations in the genome
Repairs on exonic breaks create loss-of function gene knockouts

8. CRISPR/Cas Genome Editing
CRISPR/Cas is the bacteria adaptive immune system, later introduced in other organisms

9. Genome-Wide CRISPR/Cas9 Knockout Screens
gRNA fold change = log2(Count(t)/Count(0))
Negative selection yields essential genes
Positive selection yields growth repressive genes
Identify cell-specific and condition-specific essential genes and biomarkers of drug response & resistance
Shalem & Zhang, Nat Genet, 2015

10. MAGeCK Findings on Published Screens
Wang et al
Science 2014
Shalem et al
Koike-Yusa et al
NBT 2013
MAGeCK: over 1,900 download

11. Final Exam Tue 4/26, 11:30am-1pm, Science Center 309A.
Open notes / open computer, but please don’t print and don’t cheat!
Last HW out now and due next Tue
Class participation
ScreenCast video (optional)