What do Pigeons, Single cell sequencing and Dark Matter have in common? Find out on today’s episode of Serving of Science!
It’s Day 2 of AGBT and I can’t even begin to tell you about all the amazing talks I’ve heard so far which included topics about pigeons, single cell sequencing, and Microbial Dark Matter, so without further delay – let’s get right into it.
The first plenary session had some amazing talks and the ones that spoke to me were talks from Sam Aparicio of the British Colombia Cancer Research Center and Luis Diaz of Johns Hopkins Hospital.
We understand today that cancers are heterogenous. Over time, certain clones may evolve to resist drugs or evade immune cells and there is spatial variation in how these genetically different clonal populations are distributed. Sam Aparicio discussed the use of single cell sequencing to understand tumor evolution and cancer biology. He also discussed experiments where fragments of biopsied tumors were implanted in mice – to 1) see if the site of engraftment matters – which it does and 2) how stable these xenografts are over time – stability depended on the initial selection of mutations in the clones. Single cell sequencing has given insights into the complexity of these tumors and what’s amazing is that in less than a decade we’ve gone from sequencing bulk cells and large chunks of tumors to sequencing single cells to understand the role and biology of these single cells that make up the tumor mass.
Today, we have the most comprehensive view of the coding regions of most human cancers via exome sequencing, but the problem is – how do we make sense of all this information – how do we put this knowledge to something usable. Luis Diaz‘s talk emphasized the use of knowledge and technology to understand and study recurrence. He summed up his talk by saying we are more limited by biology than technology. Which, if you think about… is a pretty interesting place to be at.
The primary focus of the morning session was to better understand cancer and tumor biology and how we can leverage knowledge and advances in current technology to better assess the state of the tumor after resection or chemotherapy.
The afternoon sessions focused on evolutionary genomics, ancient DNA, and population genetics – again with some amazing talks, but the talks I really liked were those given by Beth Shapiro from the University of CA Santa Cruz and Eddy Rubin of DOE Joint Genome Institute.
I just love Beth Shapiro – she cracks me up every time I listen to her. Her talk focused on sequencing the genome of the once abundant, yet now extinct Passenger Pigeon. Because there was no reference genome of this species, they decided to use the reference genome of a close relative – the band tailed pigeon. What was really interesting was that the mtDNA of the passenger pigeons showed no diversity, which was strange, although their genomic DNA showed tons of diversity – especially at the ends of the chromosomes, while the middle was not as diverse, which suggests possible recombination at the ends of chromosomes. It’s just amazing that technology today is helping us understand and put together these puzzle pieces and make sense of an event like never before.
Eddy Rubin’s talk I think was my favorite. His talk focused on looking at the microbes that we cannot culture in the lab – which is about 98% and that’s a lot. He first talked about generating complete draft genomes of uncultured bacteria using whole genome microbial sequencing. What followed is just amazing. He observed that while UGA codon is a stop codon in most bacteria, in some bacteria this stop codon now coded for an amino acid – Glycine – this is just mindboggling. This just added complexity to the already complex genome. Eddy then talked about Kryptonia, which are microbes found in hot springs – until today traditional 16S metagenomic sequencing didn’t pick up them up in environmental surveys, because Kyrptonia had mismatches in the universal 16S primer site – WOW… I mean I really wonder how many such microbes we’ve yet to uncover. Finally Eddy ends by saying that the holy grail of biology is not finding Yeti or the Lockness Monster, but to identify a new domain of life – which will help us understand how we evolved.
I also had a chance to attend the concurrent sessions later in the day where the focus was on single cell transcriptomics and epigenetics. Here are some highlights:
- Sten Linnarsson from Karolinska Institute discussed how we can capture the brain’s complexity, cell-cell interaction and communication by sequencing single cells. Using single cell sequencing he was able to identify that radial glia are able to differentiate into three different cell types. Neurons are vastly more complex and diverse than other organs. Single cell sequencing is capable of classifying new cell types, dynamics of cell evolution, and the putative interactome. Sequencing single cells is an emerging and powerful technique that not only gives information about the cell itself, but also spatial information and how that cell reacts to its extracellular matrix.
- Chia-Lin Wei of Lawrence Berkeley National Laboratory talked about the complex chromatin structure within the nucleus and how it is compartmentalized. She used an approach called Chia-PET to capture interacting complexes and study the interacting chromatin complex. She further discussed the impact and interaction between epigenetic modifications, non-coding elements, and polycomb group proteins.
- Max Seibold of National Jewish Health performed large scale single cell transcriptomics of the human airway epithelium. He discussed how single cell sequencing gives information about the diversity of the cells that make up the human airway epithelium. With such information we can further study the impact of environmental factors and lifestyle (smoking, pollution, etc) on gene expression. Max was also able to identify that cells previously thought to be terminal are actually plastic in nature.
- Mohan Bolisetty from the Jackson Laboratory talked about alternative splicing in RNA. ~7 annotated isoforms per gene and over 80-90% of the genome encodes for multiple isoforms. There is tissue specific and cell-specific alternative splicing. In Drosophila, Dscam1 encodes for 38,016 isoforms using mutually exclusive exon splicing (MXE). Mohan discussed how current technology has allowed him to study alternative splicing and quantify isoforms.
- Masako Suzuki of the Albert Einstein college of Medicine discussed DNA methylation and her talk focused on how representing DNA methylation in percentages doesn’t provide information of the variation in methylation at CpG sites – whether the methylation is uniform or stochastic is lost. Masako suggested an additional metric – Methylation Entrophy. Methylation entrophy is a metric that provides information about how uniform or stochastic DNA methylation is throughout the CpGs in the target region tested. Such a method will better help us represent DNA methylation.
I can’t tell you how exciting this experience has been so far and I can’t wait to tell you about the next sessions. I’d be more than happy to answer your questions, so please ask away in the comments section below! Remember to follow me on the Behind the Bench blog and Twitter.
*For Research Use Only. Not for use in diagnostic procedures