class: center, middle, inverse, title-slide # .huge[My journey through genetics:] ## …wetlab to cafe… ###
Dr Miles Benton
Senior Scientist Bioinformatics, ESR
### (4
th
August 2018) --- class: middle # .center[Advocate for reproducible research...] ## .center[Where possible my presentations and code are available online] <br /> <p> .center[ <img src="images/github_logo.png" style="width: 520px; margin-right: 1%; margin-top: 1.5em;"/> <img src="images/sirselim_qrcode.png" style="width: 202px; margin-right: 1%; margin-top: 1.5em;"/> ] </p> <br /> .center[[sirselim.github.io/presentations](http://sirselim.github.io/presentations)] --- class: middle inverse # Me... --- layout: false background-image: url("images/taranaki.jpg") background-size: cover --- class: middle <p> .center[<img src="images/house.jpg" style="width: 75%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> --- class: middle <p> .center[<img src="images/building.jpg" style="width: 75%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> --- class: middle inverse # Undergrad (2004 - 2007) ## Victoria University of Wellington (VUW) ### <span style="color:#3498DB">BBMedSci (Human Genetics, Molecular Pathology)</span> --- layout: false background-image: url("images/dna.jpg") background-size: cover --- class: center ## Human Genome Project (1990 - 2003) <p> .center[<img src="images/damn_hackers.jpg" style="width: 35%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> <p style="font-size: 14px"> .center[ <a href="http://humangenomeproject.yolasite.com/impact.php" target="blank">http://humangenomeproject.yolasite.com/impact.php</a> ] </p> --- class: middle ### The Human Genome - ~3 billion base pairs (A, T, C, G) - organised into 23 pairs of chromosomes - it took ~13 years to 'complete' the genome project - at a cost of $3 billion USD + yep, that's a $ per letter! <br> .center[**Remember a few of these stats, we'll revisit later on...**] --- class: middle inverse # MSc (2007 - 2009) ## Environmental Science and Research (ESR) & VUW ### <span style="color:#3498DB">Started off as Cell and Molecular Biology...</span> --- class: middle inverse <p> .center[ <img src="images/rod.jpg" style="width: 202px; margin-right: 1%; margin-top: 1.5em;"/> <img src="images/geoff.jpg" style="width: 202px; margin-right: 1%; margin-top: 1.5em;"/> ] </p> --- class: middle # Mitochondria - and their DNA! --- class: middle inverse ### Seven daughters of Eve (Bryan Sykes) <p> .center[<img src="images/eve.jpg" style="width: 25%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> .center[.small[*First PCR machine (cool story!)]] --- class: middle <p> .center[<img src="images/mt_process.png" style="width: 75%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> --- class: middle <p> .center[<img src="images/mt_dna.png" style="width: 55%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> --- class: middle ## My Masters project * We performed the first complete mtDNA sequencing in NZ Māori: * population genetics (more diversity) * health outcomes (some interesting results) <br> * Using a technology called a microarray * turns out this was 'flawed' and the software was TERRIBLE * so I had to improvise/'hack' --- class: middle <p> .center[<img src="images/chip_process.png" style="width: 70%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> --- class: middle <p> .center[<img src="images/gel.png" style="width: 45%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> --- class: middle <p> .center[<img src="images/seq.png" style="width: 45%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> --- class: middle <p> .center[<img src="images/bad_seq.png" style="width: 50%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> --- class: middle <p> .center[<img src="images/nj_tree.png" style="width: 70%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> --- class: middle inverse .large[The introduction of this <span style="color:#3498DB">*in-silico*</span> aspect into my project really grabbed me...] <br> .large[...so I started making the move from the wetlab/bench...] <br> .pull-right[.large[...to <span style="color:#3498DB">computers</span>...]] --- class: middle <p> .center[<img src="images/wetlab.jpg" style="width: 75%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> --- class: middle inverse # PhD (2010 - 2014) ## Griffith University, Gold Coast, Australia ### <span style="color:#3498DB">Bioinformatics (*using computers to solve biological problems*)</span> --- class: middle inverse <p> .center[ <img src="images/lyn.jpg" style="width: 200px; margin-right: 1%; margin-top: 1.5em;"/> <img src="images/rod.jpg" style="width: 222px; margin-right: 1%; margin-top: 1.5em;"/> <img src="images/donia.jpg" style="width: 170px; margin-right: 1%; margin-top: 1.5em;"/> <img src="images/geoff.jpg" style="width: 222px; margin-right: 1%; margin-top: 1.5em;"/> ] </p> --- <p> .center[<img src="images/stuff.gif" style="width: 65%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> <p style="font-size: 14px"> .center[ <a href="http://biocomicals.blogspot.com/2011/05/thats-what-bioinformaticians-do.html" target="blank">http://biocomicals.blogspot.com/</a> ] </p> --- class: inverse middle .large[...it starts with...] # NORFOLK ISLAND --- class: middle inverse <p> .center[<img src="images/NorfolkIsland.png" style="width: 70%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> --- class: middle inverse <p> .center[<img src="images/vic_england.jpg" style="width: 45%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> --- class: middle inverse <p> .center[<img src="images/sun_island.jpg" style="width: 75%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> --- class: middle center
--- class: inverse middle center <p> .center[<img src="images/NI_ped_mt.png" style="width: 100%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> 40% of current population haplogroup <span style="color:lightblue">B4a1a[...]</span><br /> <p style="font-size: 14px">Benton MC <i>et al.,:</i> <a href="https://investigativegenetics.biomedcentral.com/articles/10.1186/s13323-015-0028-9" target="blank"><i>“Mutiny on the Bounty”: the genetic history of Norfolk Island reveals extreme gender-biased admixture.</i></a> Investigative Genetics 2015, 6:11.</p> --- class: middle .center[.large[Specific female mtDNA trees]] <p> .center[<img src="images/ped1.png" style="width: 80%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> --- class: middle .center[.large[Specific female mtDNA trees]] <p> .center[<img src="images/ped2.png" style="width: 80%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> --- class: middle .center[.large[Specific female mtDNA trees]] <p> .center[<img src="images/ped3.png" style="width: 80%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> --- class: inverse ### <span style="color:lightblue">My PhD took me from basic GWAS...</span> <span style="color:#3498DB">**Benton MC**</span>, Lea RA, <span style="color:#3498DB">**Macartney-Coxson D**</span>, Carless MA, Bellis C, Hanna M, Eccles D, Chambers GK, Curran JE, Blangero J and Griffiths LR. (2015) *Serum bilirubin concentration is modified by UGT1A1 Haplotypes and Influences Risk of Type-2 Diabetes in the Norfolk Island Genetic Isolate*. **BMC Genetics** 16(1) [[article]](http://www.biomedcentral.com/1471-2156/16/136) -- ### <span style="color:lightblue">through integrative 'omics...</span> <span style="color:#3498DB">**Benton MC**</span>, Lea RA, <span style="color:#3498DB">**Macartney-Coxson D**</span>, Carless MA, Göring HH, Bellis C, Hanna M, Eccles D, Chambers GK, Curran JE, Harper JL, Blangero J and Griffiths LR. (2013) *Mapping eQTLs in the Norfolk Island Genetic Isolate Identifies Candidate Genes for CVD-risk Traits*. **American Journal of Human Genetics** 93(6): 1087-99 [[article]](http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3853002/) -- ### <span style="color:lightblue">and the application of 'outside-of-the-box' statistical approaches...</span> <span style="color:#3498DB">**Benton MC**</span>, Lea RA, <span style="color:#3498DB">**Macartney-Coxson D**</span>, Carless MA, Göring HH, Bellis C, Hanna M, Eccles D, Chambers GK, Curran JE, Harper JL, Blangero J and Griffiths LR. (2015) *A phenomic scan of the Norfolk Island genetic isolate identifies a major pleiotropic effect locus associated with renal disorder markers*. **PLoS Genetics** 11(10) [[article]](http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005593) --- class: middle # so bioinformatics also means <span style="color:#3498DB">'freedom'</span>... --- layout: false background-image: url("images/coffee.jpg") background-size: cover --- class: middle inverse # PostDoc (2014 - 2018) ## Queensland University of Technology, Brisbane, Australia<sup>*</sup> ### <span style="color:#3498DB">Research Fellow</span> ---- <sup>*</sup>but I worked remotely (from home/Wellington) - that freedom again! --- layout: false background-image: url("images/x10.png") background-size: cover --- class: top <br> # Whole Genome Sequencing .center[.large[let's revisit the idea of time and cost...]] -- * can now do a genome in <span style="color:#3498DB">**<24 hours**</span>... * ...for <span style="color:#3498DB">**~$1000 USD**</span> <br> -- # Norfolk Island Whole Genome Sequencing * sequenced 108 individuals -- * progress to date: * founder variants * glaucoma --- class: middle <p> .center[<img src="images/proton.jpg" style="width: 65%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> --- layout: false background-image: url("images/proton2.jpg") background-size: cover --- class: middle # Diagnostics Lab .large[Gene panel and Exome Sequencing (accredited - neurological disorders)] <br> ## VCF-DART (my pipeline) * used to manually work through 30-60K rows of data in excel! * could take 4-8 weeks to identify and validate variant(s) <br> * now can have a short list of variants in <span style="color:#3498DB">**1 day**</span> * validation in <span style="color:#3498DB">**<2 weeks**</span>! --- class: middle inverse # The next "big" thing in <span style="color:#3498DB">next-generation sequencing</span>? --- class: middle <p> .center[<img src="images/nanopore.jpg" style="width: 65%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> --- class: middle <p> .center[<img src="images/nanopore2.png" style="width: 65%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> --- class: middle <p> .center[<img src="images/nanopore_family.jpg" style="width: 65%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> --- class: middle inverse # Epigenetics <br> .large[<span style="color:#3498DB">the punctuation of the genome</span>] --- class: middle <p> .center[<img src="images/grandma.jpg" style="width: 25%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> --- class: middle <p> .center[<img src="images/methylation.png" style="width: 80%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> --- class: middle inverse # Methylation and Aging --- class: middle <p> .center[<img src="images/aging_paper.png" style="width: 65%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> --- class: middle inverse <p> .center[<img src="images/aging.png" style="width: 60%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> --- class: middle inverse # ESR (July 2018 - ) ## Wellington (Porirua), NZ ### <span style="color:#3498DB">Senior Scientist Bioinformatics and Data Science</span> --- layout: false background-image: url("images/desk.jpg") background-size: cover --- class: middle # I now have students of my own! <br> ## <span style="color:#3498DB">Martha Aquino</span> (Honours, QUT) <br> ## <span style="color:#3498DB">Alessandra Santana</span> (PhD, UoO & ESR) --- class: middle inverse <p> .center[<img src="images/jamie.jpg" style="width: 45%; margin-right: 1%; margin-top: -0.5em; border: 3px solid white;"/>] </p> --- class: middle inverse <p> .huge[.center[<b>Thank you!</b>]] <br> </p>