Manolis Kellis - Darwin Day - Purchase University - February 9, 2021

Relevant links:
EpiMap: http://compbio.mit.edu/epimap/
My machine Learning in Genomics Course: https://www.youtube.com/playlist?list=PLypiXJdtIca6dEYlNoZJwBaz__CdsaoKJ
Longer version of my current research: https://youtu.be/MEFQvHYLWB4 (mins 51-54 here)
More on Comparative Genomics: https://www.youtube.com/watch?v=gLZsxT42pHw (min 55 here)
Longer version of our SARS-CoV-2 and Covid-19 work: https://www.youtube.com/watch?v=eohJf6pnBic (mins 55-57 here)
Playlist with various research talks I've given: https://www.youtube.com/playlist?list=PLypiXJdtIca5NiPAinz6NsUQh3v2DVUSv

Outline:
0:00 Welcome
9:27 Intro and Dedication
11:27 Genetic Variation and Disease Predisposition
16:19 Coding vs. Non-coding Variation and Mechanism
20:09 Inheritance and Evolution: Ancient foreshadowings
22:55 Lamarck: Transmutation, Complexity force
23:29 Darwin: Random Mutation, Natural Salection
26:52 Mendel: Genetics, Discrete inheritance
29:39 Biometrics: Continuous phenotypic variation
31:19 Fischer: Polygenic inheritance of seemingly-continuous traits
31:52 Molecular basis for inheritance: chromosomes, DNA structure
32:58 Linkage, genetic mapping, Mendelian traits
34:51 Human Genome Project, Haplotype Blocks, Common Variants
36:52 GWAS (Genome-Wide Association Study) Manhattan Plot
39:27 Challenge of Uncovering Mechanism of Genetic Loci
40:56 Methods for Dissecting Disease Mechanism
42:03 Epigenomics for regulatory region annotation
44:19 Circuitry of disease loci: regulators, enhancers, motifs, cell types, target genes
45:41 EpiMap and Circuitry of 30,000 loci compbio.mit.edu/epimap
46:15 FTO Obesity Locus circuitry: IRX3/IRX5, ARID5B, Thermogenesis
48:45 Manipulate Circuitry to Reverse Disease Phenotypes
51:01 Inferring driver tissues: Alzheimer's and immune cells
51:40 Coronary Artery Disease Partitioning
51:58 Intermediate molecular phenotypes
52:16 Single-cell dissection of Alzheimer's Disease
53:17 Single-cell dissection of Scizophrenia
54:29 Brain: Spatial transcriptomics, microglia subtypes
55:15 Comparative Genomics for pinpointing regulatory regions
55:27 SARS-CoV-2 comparative genomics: non-coding vs. coding
56:33 Covid-19 pandemic evolutionary rates, variant evolutionary context
57:33 Acknowledgements, Interdisciplinary Collaborations, Organizer Thanks
59:29 Q1: Preferred coding language: Python
1:00:26 Q2/Q3: Delivering Drugs and Therapeutics
1:04:43 Q3: Regulatory Regions controlling Multiple Target Genes
1:06:19 Q4: Ethics of knowning/sharing own genome and privacy
1:10:04 Q5: Gut microbiome and disease: Obesity, Alzheimer's
1:12:05 Q6: Predisposition, Prevention, Insurance non-discrimination, Universal Coverage
1:18:00 Q7: Intervention, Side-Effects, Clinical Trials
1:20:39 Q8: Pathogen Response, Alzheimer's, Amyloid, Covid-19, Flu, Parkinson's
1:27:00 Q9: Path to Math, Engineering, CS, Evolution, Genomics, Drosophila, Friends
1:36:20 Q10: Pre-transcriptional vs. post-transcriptional variant action on disease
1:44:10 Q11: Publicly available models, tools, datasets, lectures, knowledge, Kipoi
1:50:20 Goodbyes

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