Personal genome citizen science

Enough people are in possession of SNP genotype data from direct-to-consumer genomic services (e.g., 23andme, deCODEme, Navigenics) that collaborative citizen science genomics is starting to make sense. Participants could contribute genotype data for individual SNPs or their genotype data file (600,000 – 1 million SNPs) to secure peer collaboration platforms, with different levels of permissioning to different groups of ‘gene friends.’

Personal genome citizen science could be carried out in a number of domains ranging from ancestry to health to athletic performance. Research could both replicate and extend existing academic studies and look for new associations between genomic profiles and disease. Citizen scientists could explore and identify different kinds of phenotypic data to collect and apply in attempts to make genomic data meaningful and useful. The proven benefits of opening up datasets to the wisdom of the crowds could be expected with open personal genome research too.

Personal genome citizen science examples taken from the DIYgenomics Citizen Genomes Project list:

• One fun citizen science genomics project could be applying the information in the WIRED article “Don’t tell Geico, you may be a natural born bad driver.” DIY scientists could look up their genotype value for the relevant SNP (rs6265) on the BDNF gene and match this with actual driving records.
• Another project a Silicon Valley-based DIYbio team is starting to look into is Vitamin B12 deficiency. The two relevant SNPs on the MTHFR gene, rs1801133 and rs1801131, are genotyped by 23andme and maybe also by deCODEme and Navigenics. The first step is looking up genotype values for these SNPs, (AG and GT for one participant, for example). For more information on being a peer participant in this study, please contact m AT melanieswan.com
• A third opportunity concerns the application of existing genetic association studies to peer cohorts. For example, the long-awaited results from a Boston University centenarian study were presented in November 2009. Part of this study found 18 SNPs on the ADARB1 and ADARB2 genes for RNA editing associated with centenarians. Citizen scientists could identify individuals with the favorable genotypes for these SNPs and investigate whether these people have corresponding lack of phenotypic biomarkers of aging.
• Even better than having low-cost DNA sequencing tests for consumers would be being able to self-genotype in DIYbio labs. An early example of this was Katherine Aull genotyping herself for hemochromatosis.

Individuals to drive personalized medicine era

The Personalized Medicine World Congress held January 19-20, 2010 in Mountain View, CA was one of the first business conferences devoted to personalized medicine. There is a lot of excitement about personalized medicine and genomics given some recent announcements regarding whole human genome sequencing. First, Complete Genomics reported the costs of consumables (required chemical reagents), dropping to $4,400, and even $1,500 (Supporting Online Material page 27) per genome. Illumina similarly announced dramatic price drops, an estimated all-in cost of $10,000 per whole human genome with the new HiSeq 2000 machine. Illumina currently charges individuals $48,000 for whole human genome sequencing. The HiSeq 2000 is priced at $690,000 per machine and BGI (formerly the Beijing Genome Institute) has ordered 128.

Complete Genomics’ CEO Cliff Reid made an interesting point that despite genomic sequencing having been progressing at 10x improvements per year since 2006, theoretical limits are starting to be reached and the industry will probably return to regular Moore’s Law progress curves (18 month performance doublings). While third-generation sequencers such as Complete Genomics (using a short-read sequencing-by-probe-ligation technology) and Pacific Biosciences (using a single-molecule real-time sequencing by synthesis technology) may start to reach limits, fourth-generation sequencers using other technologies such as nanopores (e.g., Oxford Nanopore Technologies), and electron microscope imaging (e.g., Halcyon Molecular, ZS Genetics), may be able to keep the sequencing industry progressing at faster-than-Moore’s-Law rates.

The most hopeful comments came from Esther Dyson and Leroy Hood. Esther Dyson, pointing out the still heavy focus on health institutions rather than consumer-empowerment for transformation to the personalized medicine era said that she felt like she was “representing the PC world at a mainframe convention.” Directly paralleling the current medical system, she also noted that when Gutenberg arrived with the printing press, the priests said ‘there’s no reason people need to read the bible themselves, we can read it for them.’ However, as shown in Figure 1, personalized medicine is about wellness, not disease, and while there are certainly overlaps with the current domain of physicians, there may be minimal encroachment due to automated tools and new health ecosystem participants such as wellness advisors.

Figure 1. Wellness becomes the domain and responsibility of the individual

Leroy Hood set forth a detailed plan for the future of medicine, P4 Medicine: medicine that is predictive, personalized, preventive, and participatory. Looking for the fingerprints of health vs. disease, he envisions a future where billions of data points are investigated per individual. There could be at least four relevant data sets. One data set is the whole human genome sequence. Another could be a biannual wellness screen for 2,500 blood-based organ-specific proteins indicating possible precursors to disease. A third data set could be an immune system screen of the 10,000 B cells and 10,000 T cells, looking at the functional regions of immune receptors, and past and preset immune responsiveness. A fourth data set, in the instance of cancer, could be taking a single cancer call and sequencing 1,000 transcriptomes simultaneously to understand how cancer is expressed in particular individuals. These data sets could help to realize medicine as an information science and address the specificity of disease and wellness in individuals.

How Daemon/Freedom is starting to happen

The books by Daniel Suarez, Daemon and Freedom, portray a possible extension of the world of today. Some elements contemplated in the books are obviously already in place such as worldwide gaming communities like World of Warcraft (11 million subscribers as of December 2008) and other MMORPGs. Botnetting of government and corporate computers is another existing feature of the contemporary world. High-magnitude financial crises (e.g., 2008) and dissatisfaction with the way they are handled is another obvious parallel, with grassroots responses such as the Move your Money movement to use local banks that did not receive bailout funds.

At a broader level, one of the most interesting ways that fundamental economic transformation could happen is the way that humans worldwide are starting to behave like a vast complex adaptive system (CAS).

1) Location-based services check-ins
Mobile-device users are checking in at the different physical locations they visit using FourSquare, Loopt, and other location-based services (LBS). People are shifting their physical-world behavior to unlock certain badges and points. In addition to earning badges and mayorships for the number of check-ins to a particular location, opt-in communities could develop using LBS platforms to award the type of check-ins, giving points and badges for behavior valued by the community. FourSquare's API is available and new applications are already being created. A simple example of rewarded behavior would be receiving double points for gym visits, escalating levels over time as visits accumulate. Another example for certain user communities might be earning double points for check-ins at local coffee shops vs. Starbucks. Starbucks actually comprises over 30% of all check-ins for LBS service Loopt.

Not just the geographical location, but also the type of activities could be rewarded. For example, there could be creativity, collaboration, learning, and teaching badges from check-ins at places like the TechShop, BioCurious, Hacker Dojo, or the Hub (social venturing collaboration). There could be time and location tagging for event attendance interpolation. Not every user would want this detail or would make their activity public, but this functionality could be useful for life-logging too. There could be sensors on public transit registering user behavior or some other way to ‘check in’ to transportation-based behavior.

There could be both incentives for positive behavior and disincentives for negative behavior. For example, users could receive points for not doing behaviors like checking in at fast-food restaurants, not going to gas stations (congratulations, you only went to a gas-station once this month!). A trustable automated check-in system could provide behavior validation, although there are obvious hacks such as not bringing the mobile device when going to fast-food locations. Finally, the spirit of incentivized check-ins should be opt-in, fun, and empowering, not didactic.

2) Real-time economy feeds
A second interesting complex adaptive system element that is arising is a real-time economy feed in the form of Blippy. Parts of the feed are publicly open and other parts just to the user community. The feed provides immediacy, transparency, and detail regarding economic activity, like real-time game-like granularity. Features could be added for zooming into views of more or less detail (e.g., real-time to-date, Amazon’s sales are down this month vs. last month). The user community can comment and interact around specific purchases.

In addition to the democratic openness of a real-time economy feed, this platform could be used the same was as LBS check-ins to reward certain behaviors. Blippy users could earn points for certain types of purchases, like carbon-neutral products certified by GoodGuide, Green Home, or ClimateCooler. Lower energy usage could be rewarded. With detailed purchase granularity, behavioral goals could be facilitated (e.g., Congratulations, you did not buy cigarettes this month! Congratulations, you bought less ice cream this month!)

3) DIYBio email list
A third fascinating development of humans as a complex adaptive system for change is the DIYbio movement. DIYbio is a worldwide self-sustaining collaborative community arising to build a new or complementary scientific order in biology. The story is told through these snippets of recent postings…

• DIYbio meeting Wednesday Jan 13th at 7PM: So all the DIYbio groups have hacked 300X microscopes out of $7 webcams.
• Plant stilbenes, SIRT1 activators; request for assistance: Hi, I am looking for tropical crop plants that produce phytoalexins called stilbenes; phenolic chemicals, that among other things, include molecules that activate the SIRT1 deacetylase. For the moment I am restricting my search to plants of the Fabaceae subfam. Faboideae (pea group). Currently, I am looking at the literature on Cajanus cajan (pigeonpea) & Arachis hypogaea (peanut, groundnut). I am also looking at literature on non-resveratrol stilbene activators of SIRT 1. I have linked two relevant papers for context.
• DIY movement in Shenzhen, China: I'm looking for a previous post about a DIY movement in Shenzhen, China, somebody posted it before but I can't find it now? It wasn't bio focused, more about electronics.

Aging research: systems biology, genomics and new tools

Three important themes emerged from the Buck Institute’s Systems Biology Symposium of Aging held November 10-13, 2009. The themes were progress in the overall understanding of aging as a systems biology problem, the role of genomics in aging, and new tools development for aging research. Happily, some immediately applicable tidbits were discussed: the findings of the protective response of endurance exercise, and the use of resistance exercise as a countermeasure to sarcopenia. (Mark Tarnopolsky)

Theme 1: Aging is a systems biology problem
Inflammation
Increasingly, aging is being understood as a systems biology problem involving cascades of signals across multiple pathways, many of which break down with aging. In younger organisms, problems are managed automatically as they arise, but in older organisms, the resolution processes do not work as well. When cells become damaged as a consequence of aging, they can either self-destruct through apoptosis (regulated cell death) or become senescent (living on without dividing). Senescent cells persist in tissues, where they may secrete inflammatory proteins. Many major age-related diseases, including atherosclerosis, heart attack, stroke and metabolic syndrome, share an inflammatory pathogenesis. The build-up of senescent cells can lead to both degenerative disease (aging) and hyper-proliferative disease (cancer). There are some efforts underway to facilitate the removal of senescent cells, for example, using an MMP inhibitor to kill senescent cells.

Dynamic regulatory continua
It is being suggested that more and more aspects of living systems such as humans are dynamic regulatory continua, and that there may be optimum points on the continuum which become harder to maintain with aging. One example of a dynamic regulatory continuum is the interrelation of cholesterol, fats, and Alzheimer’s disease. Having lower levels of the 142 alpha-beta plaques is neuroprotective, for example, but higher levels become harmful. One technique for understanding dynamic regulatory continua is to look at explaining the events at one biological level in terms of the events at the levels above and below them. (John Tower)

Signaling pathways
There is more of an effort to examine whole processes such as pathway networks and the chain of events in DNA transcription and translation. Current knowledge of signaling pathways is fairly primitive. The role of mRNA translation is being investigated as it is known to be related to growth promoting activities like cancer. There is the general translation of RNA, but this can be further modulated by the cell. In addition, signaling pathways are not working alone, there are probably many pathways converging. For example, there is likely cross-talk between several important signaling pathways such as the insulin pathway, the TGF-beta pathway, the IGF-1 pathway, and the TOR pathway. (Heidi Tissenbaum) In another example of the systemic interactions of aging, amyloid-binding compounds were found to suppress protein aggregation models in concert with homeostatic function (i.e., autophagy, chaperones, etc.). (Gordon Lithgow)

Theme 2: The role of genomics in aging
As with many areas of biology and medicine, the role of genomics is becoming increasingly important in aging. While it is known that there is little variation (0.1%) among SNPs in human genomes, 12% of the genome may vary structurally (copy-number variations, deletions, inversions and insertions of genes). On the threshold of whole human genome sequencing, it is being realized that SNP data alone is insufficient for a genomic understanding of health; more levels of data and annotated data, potentially including RNA sequencing to see protein expression will be needed. (Mike Snyder)

Variation in genomes
Three areas of research were presented regarding genome variation and aging. First were the long-expected results of Boston University's genome-wide association study (GWAS) on centenarians. The study found 150 SNPs in the genetic signature of longevity, 33 of which meet genome wide significance and are replicated. The most important longevity genes, most already associated with aging pathways, were: IL7 (immune system), CDKN2B (tumor suppressor), and APOE, CTNNA3, TOMM40, SORCS1, and SORCS2 (Alzheimer’s disease). (Tom Perls)

Related results were confirmed by personal genomics company 23andme. A study of senior athletes found that this cohort exhibited lower risk than the database in general. Ten chronic disease conditions were reviewed including coronary artery disease, breast cancer, prostate cancer, heart attack, type 2 diabetes, high blood pressure, high cholesterol, and macular degeneration. (Joanna Mountain) However, other research found that there is not a full overlap between genes conferring longevity and genes conferring increased healthspan. (Monica Driscoll)

Variation in genomic expression
Four interesting research findings found variation in genomic expression between older and younger organisms. First, another centenarian study found significant diversity of microbial communities in different age groups. For example, there was a high level of expression of certain miRNAs in older livers (miRNA-200c, miRNA-141, and miRNA-31). (Claudio Franceschi) A second study found that a full third of genome expression changed with age in worms. (Simon Melov)

A third study found a general relaxation in translational control and protein production during aging. It was proposed that increased or sloppy protein expression might contribute to proteotoxicity. (Monica Driscoll) Applying a systems biology and network analysis approach, a fourth study looked at how the structure of biological networks declines with age. The AGEMAP (a gene expression database for aging in mice) was reviewed, finding 26% fewer edges (edge nodes on the network) in 24 month old mice vs. 16 month old mice. It is possible that gene expression networks could lose integrity with age. An unexplored but possible explanation is that if there if less transcription, then network edges disappear. (Daniel Promislow)

Theme 3: New tools development for aging research
New approaches and tools are critical to advancing the study and potential remedy of aging, and three interesting talks were presented. First, progress in microfluidics and microscopy was discussed, particularly an exceptional development in electron microscopy that may allow the noninvasive molecular-resolution imaging of live samples (Figure 1). Usually electron microscopy is a destructive technique as the electron beam destroys the sample in the process of inspecting it. (paper: Noninvasive Electron Microscopy with Interaction-free Quantum Measurements). (Fatih Yanik)

Figure 1: In vivo noninvasive molecular imaging.

Image credit: http://www.rle.mit.edu/bbng

A second area of improvement has been in the targeted analysis of specific proteins. Now that there are robust measures for mRNA, proteins and post-translational modifications are the next areas of interest. Traditional shotgun analysis techniques are being improved upon by targeted analyses of specific proteins using mass spectrometry. The process is to take a protein mixture, produce peptides through proteolysis, collect a snapshot of multiple peptides at once, and use mass spectrometry to separate them by their mass. This method greatly expands protein identification and analysis capabilities, including the ability to do time course experiments. (Mike MacCoss)

Third, a genomic database tool, PharmGKB, was presented. The database facilitates a systems approach to pharmacology. Researchers can search for pharmacogenes, for example, given a drug and putative indication, ranking all genes in the genome for the likelihood of interactions. The database contains information regarding over 500 drugs, 500 diseases, and 700 genes with genotyped variants as of November 2009. (Russ Altman)

Top 10 technology trends for 2010

Some of the freshest ideas in 2009 were botnet futures (Daemon, Daniel Suarez), a variety of neuro scanning applications (The Neuro Revolution, Zack Lynch), a systems approach to Earth (Whole Earth Discipline, Stewart Brand), accelerating economic development through charter cities (Charter Cities, Paul Romer), automatic markets for fungible resource allocation (Broader Perspective, Melanie Swan), and the notion that the next-generation of technology needed to solve intractable problems could be non-human understandable and come from sampling the computational universe of all possible technologies (Conversation on the Singularity, Stephen Wolfram).

Heading into a brand new decade, there are several exciting technology areas to watch. Many are on exponential improvement curves, although from any viewpoint on an exponential curve, things may look flat. Most of this blog’s big predictions for 2009 came true. Here’s what could happen in the next year or so:

1. Closer to $100 whole human genome
Third-generation DNA sequencer Pacific Biosciences estimates that they are still on track for a late 2010 release of single-molecule real-time sequencing technology that could eventually lead to less than $100 whole human genome sequencing.

2. Mobile continues to be the platform
There will likely be a greater launch and adoption of addictive location-based services (LBS) like FourSquare, Gowalla and Loopt, together with social networking, gaming, and video applications for the mobile platform. Continued trajectory of smartphone purchases (one in four in the U.S.). iPhone and Android app downloads double again. Gaming expands on mobiles and on the console platform with Avatar and maybe other 3-D console games. Internet-delivered content continues across all platforms.

3. 22nm computing node confirmed for 2011
Intel possibly confirming and providing more details about the 22nm Ivy Bridge chip planned for commercial release the second half of 2011. The September 2010 Intel Developer’s Forum may feature other interesting tidbits regarding the plans for 3-D architectures and programmable matter that could keep computing on Moore’s Law curves.

4. Supercomputers reach 15% human capacity
Supercomputing capacity doublings have been occurring each few years and could likely continue. As of November 2009, the world’s fastest supercomputer was the Cray Jaguar, running at 1.8 petaflops (1.8 x 10¹⁵ flops), approximately 10% of the estimated compute capacity of a human.

5. Confirmation of synthetic biology fuel launch for 2011
Pilot plants are running and the commercial launch of the first killer app of synthetic biology, synthetic fuel, could be confirmed for 2011. Sapphire Energy and Synthetic Genomics are generating petroleum from algal fuel; LS9, petroleum from microbes; Amyris Biotechnologies, ethanol, and Gevo, biobutenol.

6. Smart grid and smart meter deployment
In energy, more utilities moving to deploy internal smartgrid network management infrastructure and starting to replace consumer premises equipment (CPE) with advanced metering infrastructure (AMI) for automated utility reading and customer data access. Dozens of efforts are underway in the U.S. (Figure 1).

Figure 1: U.S. Smart Metering Projects Map as of Jan. 2010

7. Increased choice in personal transportation
More electric vehicle offerings, greater launch of alternative fuels, a potential Tesla IPO announcement, and more widespread car share programs (i.e., City CarShare, Gettaround).

8. Real-time internet search dominates
More applications allow real-time search functionality through content aggregation, standards, and more granular web searches. Search could be 40% real-time, 40% location-based, 20% other.

9. Advent of health advisors and wellness coaches
Hints of personalized medicine start to arrive with the unification of health data streams (i.e., genomics, biomarker, family and health history, behavior, and environment) into personalized health management plans. Early use of health monitoring devices (i.e., FitBit, DirectLife) as a prelude to biomonitors.

10. WiMax roll-out continues
Clear adds more markets to its current 26. Increasing importance of integrated data stream management (video, voice, etc.) on fixed and mobile platforms.

Probably not happening in 2010 but would be nice…

• Kinko’s buys high-end 3-D printer (i.e., ZPrinter 650 or Dimension Elite or uPrint) and DIY product design communities go professional (i.e., Shapeways, Ponoko)
  
• Nanotechnology demonstrations of mechanical synthesis and positional assembly

Still waiting for significant progress regarding…

• 4G/LTE roll-out
• Driverless cars, on-demand personal rapid transport systems
• Ubiquitous sensor networks
• OLEDs