{"id":7720,"date":"2016-02-18T23:12:35","date_gmt":"2016-02-19T04:12:35","guid":{"rendered":"http:\/\/admin.acceleratingscience.com\/?p=7720"},"modified":"2019-03-08T03:27:34","modified_gmt":"2019-03-08T03:27:34","slug":"small-step-sequencing-agbt-2016","status":"publish","type":"post","link":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/small-step-sequencing-agbt-2016\/","title":{"rendered":"Small Step for Sequencing, Giant Leap for Science| AGBT 2016 Dispatch #3"},"content":{"rendered":"<p>Astronauts, Sea Slugs, and Rare Mendelian diseases, what do they have in common? Find out today on Serving of Science!<\/p>\n<p>It\u2019s Day 3 of AGBT, and it has been a ride \u2013 a fun ride, but a ride nonetheless. An intense schedule packed with talks that are just incredible. So, lots of coffee, lots of sugar, lots of not sleeping, and tons of amazing science talks packed with a shot of excitement and adrenaline \u2013 how does that sound?<\/p>\n<p><iframe loading=\"lazy\" width=\"760\" height=\"428\" src=\"https:\/\/www.youtube.com\/embed\/fb8Qim6FdZw?feature=oembed\" frameborder=\"0\" allow=\"accelerometer; autoplay; encrypted-media; gyroscope; picture-in-picture\" allowfullscreen><\/iframe><\/p>\n<p>Today\u2019s focus was on technology and novel applications including talks about Rare Mendelian disorders, Astronauts, and Sea Slugs.<\/p>\n<p><a href=\"http:\/\/research.fhcrc.org\/bielas\/en.html\">Jason Bielas<\/a> of Fred Hutchinson Cancer Research Center talked about how single cell RNA sequencing can help us understand complex cell populations \u2013 especially immune cells. Single cell sequencing can allow you to count cells and identify subtypes of immune cells. During his talk, he showed how adding dimension to data opened up an entirely novel way to visualize and analyze the data. When a 2D graph with colored points (denoting different cell populations and subpopulations) gets another dimension \u2013 the data suddenly comes alive \u2013 where you can explore how these cell populations spatially interact with one another and how subtypes are localized. Turning 2D data to 3D data opens up a window visualize and analyze information in an entirely new way.<\/p>\n<p><a href=\"http:\/\/www.whitney.ufl.edu\/research\/faculty\/leonid-l-moroz\/moroz-current-lab-members\/andrea-kohn-low-res\/\">Andrea Kohn<\/a> from the University of Florida described epitranscriptome as the \u201cdark matter of the genome\u201d. Her talk focused on studying neurons in sea slugs (Aplysia) where decades of research have allowed them to distinguish neurons visually. Just like DNA, RNA can have modifications, and that can alter RNA stability and basic function. She discussed RNA modifications like N6-methyladenosine, Pseudouridylation, and RNA editing. Now, what\u2019s exciting is, this is the first time it\u2019s accomplished in single neurons of sea slugs. To thoroughly understand these modifications we need to be able to go down to a single base resolution, since these may be potential biomarkers for disease or evolution.<\/p>\n<p><a href=\"http:\/\/www.gs.washington.edu\/faculty\/nickerson.htm\">Debbie Nickerson<\/a> from the University of Washington talked about rare Mendelian disorders. Of the 7440 rare Mendelian phenotypes described, we know the genetic basis for only about 3400 and every year 300 new Mendelian disease phenotypes are described. These diseases are often seen only once or very few times, which makes it very hard to study. They are also heterogeneous, where many different genes can cause the same disease, and often genetic mosaicism may play a role in these as well. Debbie\u2019s talk focused on the genetics behind these types of diseases and how a large-scale research initiative to identify genes underlying rare diseases is currently underway.<\/p>\n<p><a href=\"http:\/\/www.masonlab.net\/\">Christopher Mason<\/a> of Weil Cornell Medical College discussed the NASA twin study, where twins who are both astronauts are studied over time as one heads off into space, and the other one stays on earth \u2013 to understand what kind of effect space travel may have on our biology. Chris wants to eventually study methylation, hydroxymethylation, proteomics, microbiome, RNA expression, chromatin, B and T-cell counts, telomere counts, and much more\u2026. He wants to study the Epigenome, Epitranscriptome, and the Epiproteome \u2013 and the Epi \u2013 family continues to grow! What was fascinating about his talk, was the logistics of testing samples.<\/p>\n<p style=\"padding-left: 30px\">How do you test samples in space?<br \/>\n1) you either freeze them and send them back to earth or<br \/>\n2) you send a sequencer to space.<\/p>\n<p>So, freezing it was \u2013 frozen samples were dropped down to earth and recovered from the ocean and studied. But imagine how hard it must be to collect samples in space when you and everything around you is floating in zero-gravity. Space is a challenging environment for lab work. This study is the first pilot experiment to get things set up so that we can continue to do research and collect more robust data over time \u2013 to prepare for the day or days we may have to spend in space as we make our way to Mars. Chris concluded by saying the genome is complex and has many secrets left to be discovered.<\/p>\n<p>I also had the opportunity to attend the concurrent session (Biology) in the evening.<\/p>\n<ul>\n<li><a href=\"http:\/\/broadinstitute.academia.edu\/AlexandreMelnikov\">Alexandre Melnikov<\/a> of the Broad Institute of MIT and Harvard discussed the Malaria parasite. He discussed sequencing methods to investigate the genetic basis of drug resistance, demographic history and genomic diversity of the parasite. In a study, they could track resistance alleles and also identify other mutations in the parasite genome. Overall, they observe how drugs against the malaria parasite, have in fact created an environment that promotes natural selection and population divergence not only in the evolution of the parasite but also in the adaptation to different mosquito vectors.<\/li>\n<li><a href=\"http:\/\/www.ncbi.nlm.nih.gov\/\">Valerie A. Schneider<\/a> from the National Center for Biotechnology Information discussed curation of the human reference genome assembly. With advances in sequencing technologies and capabilities, the database is evolving. The human reference genome, which was primarily a \u201cclone-centric\u201d (Sanger) approach, is now transitioning to an \u201cassembly-centric\u201d (Next Generation Sequencing) approach. Although new technologies have allowed for faster genome assemblies, traditional genomic clones continue to play a significant role in reference assembly curation, particularly in regions associated with segmental duplications, repetitive sequence or other genomic complexities.<\/li>\n<li><a href=\"http:\/\/www.dfhcc.harvard.edu\/insider\/member-detail\/member\/peter-j-park-phd\/\">Peter Park<\/a> of the Harvard Medical discussed the importance of studying neurons individually as single cells. The brain is a complex organ, and as we dig deeper into it, we learn just how diverse and different the cells that make up the organ can be. Peter explained how analyzing cells in bulk (several cells at a time) gave an average view of the genotype or transcriptome of all those cells. We miss the genomic and transcriptomic diversity represented by each cell, unable to detect mutations, variants, isoforms, etc\u2026present in 1 or a small number of cells. Peter used Whole Genome Single cell sequencing to study neurons by amplifying the genome using techniques like MALBAC and MDA. His results show that each human cortical neuron has a unique genome harboring &gt; 1000 somatic SNVs. What\u2019s interesting is that somatic SNVs can be used to reconstruct developmental lineages of neurons. Such an approach can help us study lineages in other organs and even cancer.<\/li>\n<li><a href=\"https:\/\/www.vcu.edu\/mbg\/faculty\/buck.html\">Gregory Buck<\/a> from Virginia Commonwealth University gave a talk about the vaginal microbiome. Bacterial vaginosis may increase preterm birth and may even <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4178329\/\">increase risk of getting HIV<\/a>. He studied changes in vaginal microbiome of several women (different ethnicities and pregnant vs. not pregnant). His results show that Lactobacillus genus is broader and has a dominant profile associated with pregnancy than healthier women. His research also indicates that the vaginal microbiome is very different between women of different ethnic backgrounds. A study such as this sheds light on the importance of understanding microbiome differences between cohorts and how important sampling is, as it may skew future studies \u2013 if a broad, diverse, representative sample isn\u2019t accounted for.<\/li>\n<li><a href=\"https:\/\/users.soe.ucsc.edu\/~ed\/\">Richard Green<\/a> from the University of California Santa Cruz gave a presentation about an in vitro method similar to Hi-C. The method uses proximity ligation to study interacting pieces of the genome to understand the dynamics of the compartmentalization and chromatin, which may bring certain genomic regions together. Richard discussed how such a technique might help resolve metagenomic challenges, where vastly different organisms and genomes have to be assessed.<\/li>\n<li><a href=\"http:\/\/www.gs.washington.edu\/academics\/postdocs\/liachko.htm\">Ivan Liachko<\/a> University of Washington also discussed a method similar to that presented by Richard Green, using Hi-C to study metagenomics in mixed populations. As genomes are organized into 3D structures, the closer the sequences are next to each other, the more likely they are to interact and the likely they are to come from the same cell\/organism. Such an approach is important, especially when we study mixed microbial population where traditional methods cannot detect if two DNA fragments came from the same cell or different cell. He used this technique to sequence the starter culture of craft beer and along with the expected microbial populations, he was able to detect a new hybrid yeast. Traditional techniques would have shown there was perhaps the presence of two yeast populations. Only a method such as proximity ligation may be able to give you that kind of information and resolution, where strain information can be deconvoluted from mixed communities.<\/li>\n<\/ul>\n<p>How can you not be excited when you realize how much we have yet to uncover and how much we have yet to learn about our genomes \u2013 tends to bring out that curiosity and wonder for life we had when we were children. I am psyched to continue onto Day 4, but I will be back with updates \u2013 remember to share and to follow me on the behind the bench blog and twitter &#8211; Ciao!<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Post a comment to let me know what you think and be sure to catch recaps of <a href=\"http:\/\/admin.acceleratingscience.com\/behindthebench\/sharing-data-is-caring-agbt-2016\/?socid=social_btb\" target=\"_blank\" rel=\"noopener noreferrer\">Day 1<\/a>\u00a0,\u00a0<a href=\"http:\/\/admin.acceleratingscience.com\/behindthebench\/microbial-dark-matter-agbt-2016\/?socid=social_btb\" target=\"_blank\" rel=\"noopener noreferrer\">Day 2<\/a>, and <a href=\"http:\/\/admin.acceleratingscience.com\/behindthebench\/agbt-2016-dispatch-4\/?socid=social_btb\" target=\"_blank\" rel=\"noopener noreferrer\">Day 4<\/a> of AGBT and our complete <a href=\"http:\/\/admin.acceleratingscience.com\/behindthebench\/what-you-missed-at-agbt-2016-a-complete-recap\/?socid=social_btb\" target=\"_blank\" rel=\"noopener noreferrer\">AGBT Recap<\/a>.<\/strong><\/p>\n<p>&nbsp;<\/p>\n<p>*For Research Use Only. Not for use in diagnostic procedures<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Astronauts, Sea Slugs, and Rare Mendelian diseases, what do they have in common? Find out today on Serving of Science! It\u2019s Day 3 of AGBT, and it has been a ride \u2013 a fun ride, but a ride nonetheless. An intense schedule packed with talks that are just incredible. So, lots of coffee, lots of<\/p>\n","protected":false},"author":120,"featured_media":7730,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_kad_blocks_custom_css":"","_kad_blocks_head_custom_js":"","_kad_blocks_body_custom_js":"","_kad_blocks_footer_custom_js":"","_monsterinsights_skip_tracking":false,"_genesis_hide_title":false,"_genesis_hide_breadcrumbs":false,"_genesis_hide_singular_image":false,"_genesis_hide_footer_widgets":false,"_genesis_custom_body_class":"","_genesis_custom_post_class":"","_genesis_layout":"","_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[113],"tags":[116,74],"division":[],"class_list":{"0":"post-7720","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-events-and-tradeshows","8":"tag-agbt-2016","9":"tag-sequencing","10":"entry"},"_selected_authors":"","_selected_reviewers":"","acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO Premium plugin v27.8 (Yoast SEO v27.8) - https:\/\/yoast.com\/product\/yoast-seo-premium-wordpress\/ -->\n<title>Small Step for Sequencing, Giant Leap for Science| AGBT 2016 Dispatch #3 - Behind the Bench<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.thermofisher.com\/blog\/behindthebench\/small-step-sequencing-agbt-2016\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Small Step for Sequencing, Giant Leap for Science| AGBT 2016 Dispatch #3\" \/>\n<meta property=\"og:description\" content=\"Astronauts, Sea Slugs, and Rare Mendelian diseases, what do they have in common? Find out today on Serving of Science! It\u2019s Day 3 of AGBT, and it has been a ride \u2013 a fun ride, but a ride nonetheless. An intense schedule packed with talks that are just incredible. 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