The 1st LavaAmp prototype was shipped this week from Biodesic to Gahaga Biosciences and the process is documented and engineering details uncovered in Rob Carlson’s post.

The people behind are mainly ex SciFoo Campers and open science advocates: Guido Nunez-Mujica, Joseph Jackson, Rob Carlson, Jim Hardy and a cool engineer Rik Wehbring.

Here’s the pic of the prototype:

In the 2007 proof-of-concept paper, entitled A Pocket-Sized Convective PCR Thermocycler, authors Nitin Agrawal, Yassin A. Hassan, and Victor M. Ugaz wrote:

Herein, we introduce an innovative thermocycling system that
harnesses natural convection phenomena to amplify DNA rapidly by the PCR in a greatly simplified format. A key element of this design is an architecture that allows the entire thermocycling process to be actuated pseudo-isothermally by simply maintaining a single heater at a constant temperature, thereby enabling a pocket-sized battery-powered device to be constructed at a cost of about US$10.

Realizing the potential of the device and thinking about how to build a digital thermocontroller for it with the Arduino I contacted Victor Ugaz this January and was informed that they only built the proof-of-the-concept  devices testing them in the lab interested mainly in ‘understanding the physics of the thermally driven flow and its effect on the reaction’. But it was obvious to me that somebody will produce those devices for the market and make them affordable to people as it seemed to me as the familiar case of the low(est)-hanging-fruit.

So when Joseph Jackson mentioned to me his grandiose open science plans and the groups’  ‘super affordable pcr’ project I became instantly interested. As Rob Carlson writes:

The intended initial customers are hobbyists and schools.  The price point for new LavaAmps should be well underneath the several thousand dollars charged for educational thermocyclers that use heater blocks powered by peltier chips.

The effort will make use of existing saliva samples taken from California patients, whose average age is 65. Their DNA will be analyzed for 700,000 genetic variations called single-nucleotide polymorphisms, or SNPs, using array analysis technology from Affymetrix. Through the National Institutes of Health (NIH), the resulting information will be available to other researchers, along with a trove of patient data including patients’ Kaiser Permanente electronic health records, information about the air and water quality in their neighborhoods, and surveys about their lifestyles.

The target age group shows that the focus is on “secondary aging”:

Given the high average age of the group, the platform will also be a boon to studying diseases of aging. “One might want to ask,” Schaefer says, “what are the genetic influences on changes in blood pressure as people age, and how are those changes in blood pressure related to diseases of aging, like stroke and Alzheimer’s and other cardiovascular diseases?”

UCSF will perform separate procedures on the samples to determine the length of telomeres–sections of DNA at the ends of chromosomes that protect against damage. The length of telomeres is associated with cell division and aging. One of the coinvestigators on the project is Elizabeth Blackburn, a biologist at UCSF who shared the 2009 Nobel Prize in Medicine for her work on telomeres.

Sage Bionetworks is a not-for-profit organization developing an open-access “pre-competitive” platform for networked and annotated models of human disease. It’s a huge and unparalleled bioinformatics enterprise: starting with an anonymous $5 million donation and soon making high throughput, large-scale human and mouse biological data (largely from Merck) available in the range that’s already in the public domain today. The co-founders are real big shots, Stephen Friend, a former successful Merck Executive and Eric Schadt, now a Chief Scientific Officer of Pacific Biosciences, who is “an industry leader in network biology with a number of high-profile publications over the past 5 years that have energized the systems biology community.”

For the last couple of months there was only minimal information available on the Sage website but now scientists interested can get the big picture in more details via a significant update.

The strong motivation behind is to build an open-access standard platform for human disease biology because

human disease biology has no common languages, no accessible communal repositories and no government, corporate or foundation investment in generating an inclusive resource….The experimental data underlying disease biology, like the genome itself, needs to be open access because the data is simply the beginning of the process….

Human disease biology is so complex, interconnected and expensive to research that the existing dominant business strategies of building and patenting unique models need to be replaced by a common standard. Like the internet, disease biology models will gain strength by their very nature as public platforms for interoperability and communication – this approach is at the very heart of that strength.

At the heart of the Sage model are the so called Global Coherent Datasets that will be for the first time available for scientists working all around the world. We’re talking about a real goldmine here for researchers:And if that doesn’t sound good enough for a start then the following Sage Datasets will be available in 1 to 2 years:

• Extended D&O datasets to include >2,000 additional mouse and >1,000 additional human individuals (totals: >3,000 & >3,500 respectively)
• Extended neurological datasets for mouse to include sleep, anxiety and depression traits
• Extended CVD phenotypes for mouse and human to include additional relevant tissue-types (kidney, arterial wall, heart, plaque, etc)
• Age-related phenotypes relevant to sarcopenia (Mouse)
• Oncology datasets relevant to hepatocellular carcinoma including paired tumor/adjacent normal tissue and networks predictive of outcome. Also breast cancer and colon cancer datasets
• Human/mouse datasets relevant to respiratory and inflammatory disease

You name it.

As an approximate, working definition Global Coherent Data Sets are those “where DNA variation, genome-wide molecular phenotypes such as gene-expression, and clinical phenotypes have been measured in a sizable population of genetically diverse individuals.” Sizable: hundreds of individuals at least.

Meet the Sage Repository and Commons concepts: Sage Commons will contain the Global Coherent Data Sets, the network models derived from those sets, and the analytical methods and code used to generate the network models. Sage Repository will contain the same triplets only those “may not be annotated or coherent to the degree required for the Sage Commons, but which are nevertheless useful to the biological research community”

How can you utilize the data once it’s available starting probably 2010ish? 2 Case Studies are mentioned (identify novel target for obesity & reposition a drug) out of which I’d like to emphasize drug repurposing:

The pharmaceutical industry has an ever expanding portfolio of compounds that have been shown to be safe in human testing and to effectively modulate particular targets. In some cases these drugs show efficacy and go on to become marketed drugs whilst in other cases they may fail to show efficacy precluding their development for the selected indication. In either case there is a significant value to the industry in finding new indications for drugs with these characteristics (safe & modulate a known target) as a means to realize value on investment. Using network models tied to disease traits it is possible to generate potential new indications for compounds. Figure 2 illustrates how this was done for a compound originally developed for asthma. A molecular signature for the drug was interrogated against disease networks and a significant enrichment of the drug signature was noted for a particular pancreatic islet network linked to obesity and insulin resistance traits in a mouse F2 population. This led to the prediction that this drug may modulate these phenotypes through an effect on the islet module. This was tested in a mouse DIO model in which the compound helped normalize insulin and glucose levels.

The award goes to Elizabeth H. Blackburn, Carol W. Greider and Jack W. Szostak.

The problem of telomere/telomerases is highlighting the double but strictly related aging/cancer problem space:

Blackburn Lab

Greider Lab

Szostak Lab

“As part of our ongoing article-level metrics program, we’re delighted to announce that all seven PLoS journals will now provide online usage data for published articles”.

I downloaded the entire dataset and as a starter sorted it according to Combined Usage = numbers of HTML page views (the full text version of our articles) + PDF downloads + XML downloads

Here is the Top Ten most viewed PLoS articles according to the newly released article-metrics (read the FAQ too).

For example, consider the recent study of adenosine and sleep led by Philip Haydon and Marcos Frank at the University of Pennsylvania in Philadelphia (M. M. Halassa et al. Neuron 61, 213–219; 2009). Adenosine binds to receptors on neurons, thereby regulating neuronal signalling. Interestingly, adenosine seems to represent ‘sleepiness’: it accumulates during wakefulness and dissipates during sleep. Where does it come from? It is generated from adenosine triphosphate (ATP), which is secreted by astrocytes — a major type of glia.
Therefore, if we want to map the functional brain connections controlling sleep, we need to include glia and the extracellular space between glia and neurons. If we’re going to understand brain function by mapping the brain, we need to include most of the brain in our map.

I tried to draw an analogy between the situation in brain mapping and personal genomics on FriendFeed:

Update: it seems Dave Featherstone had something similar in mind as an analogy, he answered my email the following way:

Yeah, that’s a good analogy. The original version of my column said the connectome would be like if the human genome had only sequenced exons. But that sentence was cut for space considerations.

Last Friday 23andMe came up with Haplogroup Tree Mutation Mapper which is the first experimental feature that can be instantly tested by biogeek customers (a large portion of  the company’s customer base) in its freshly launched technology sandbox 23andMe Labs that is much like Google Labs.

Haplogroup Tree Mutation Mapper “shows you which particular mutations in a person’s mitochondrial DNA (maternal ancestry) or Y chromosome (paternal ancestry) were used to determine their haplogroup assignment.”

Basically you are picking the Y chromosome or type the name of a maternal mitochondrial haplogroup (like T) into the search box and as a result you get a list back with the position and id-s of the defining mutations. With that information you can play different genetic genealogy games if you like.

But playing with a pure textual list of SNPs doesn’t sound too fascinating and the tool is not really a “Mapper” as there’s no visualization included. Wouldn’t it be nice if you can visualize all those haplogroup defining SNP positions at once and get extra biological information on them right away? Well, you cannot do that within the 23andMe website but you can do that with Mitowheel which is a graphical representation of the circular human mitochondrial genome (Disclaimer: I am part of developer team, see post and the Mitowheel blog).

For instance the SNPs on the left are parts of the T haplogroup defining mutations used by 23andMe. The rCRS is the revised Cambridge Reference Sequence, the rs<numbers> are the reference cluster IDs of SNPs. rCRS is a reconstruction of a single European individual’s mtDNA, the source was an unnamed placenta without further identity and it contains several rare alleles. I’ve also heard rumors that some blurry nucleotides were replaced by cow DNA. The rCRS nevertheless provides a uniform nucleotide numbering scheme (0-16569) even if the 3106 position is a phantom position (like chief evangelist) as there was an incorrect duplication of 3107C in the original sequence. So if you check the rCRS positions on the list, the one you should use in Mitowheel is +1 position away that you can see in parentheses if you click on the individual SNP rsids within the 23andMe site.

So here are all the positions 23andMe is using for T haplotyping and you can type them into the Mitowheel search box: 10463, 13368, 14905, 15607, 15928, 188, 4917, 709, 8697 and step through all of them by clicking the arrow in the search box and get a lot of extra information by checking the info popup box.

As a 23andMe customer you can instantly look for functional information on your particular SNPs with Mitowheel by adding the nucleotide letters of your specific mutation to the positions like in 8697A, so the following is the result of the search for all of my T defining SNPs: 10463C, 13368A, 14905A, 15607G, 15928A, 1888A, 4917G, 709A, 8697A

As Mitowheel incorporates data on fully sequenced human mitochondrial genomes that have been deposited in the GenBank database the allele frequencies of 23andMe customers can be checked at those positions and groups can be created based on Gábor Zsurka’s, Mitowheel founder, post. Each little gray bar above or below a nucleotide letter represents the number of individuals who carry a SNP at the given position as compared to the revised Cambridge reference sequence.

The group creating search looks like the following in case of my T defining SNPs (a plus sign is added to the search items above):

+10463C, +13368A, +14905A, +15607G, +15928A, +1888A, +4917G, +709A, +8697A

A while (!) back you posted an inspiring piece linking to Harvard’s BioVisions inner life of the cell – it was 2006…It got me thinking that we could do something similarly inspiring with actual cellular images entered into our annual cellular analysis image competition. It took 2 years to make it happen, but finally:
We have just posted a social media release highlighting the winners’ images being shown on the jumbotron in Times Square, with a short narrated film about the images and what they could mean for medical research, posted on YouTube:

Video interviews with the winners in Times Square on YouTube:

Short listed entries on a public site to inspire and encourage people to share in the beauty of science.

I hope you enjoy the links – and thanks for being the initial spark of inspiration.

regards

Conor

Now imagine a mobile application/gadget-in-a-belt-pouch that is the most advanced telemedicine solution in the market. With this application/gadget you were able to non-invasively monitor vital signs of the people that matter you the most at anytime from anywhere around the world. You were able to quickly recognize life threatening heart and respiratory problems of the people you care about and maybe save their lives.

The problem is that such a product exists according to this press release (via androidguys) but you are not allowed to legally use it (no information on the details of purchase yet) unless you are a registered and licensed physician. The press release does not offer any reasonable (legal?) explanation on why this is the case.

The Dyna‐Vision© G1 Android Telemedicine Application by RS TechMedic B.V (“specialized in creating very easy-to-use user interfaces”) will be officially launched during the CeBIT starting today:

Dyna‐Vision© is a small light weight and portable device, with the dimensions of a PDA. The patient wears this device in a belt pouch. This reliable and sophisticated medical device monitors up‐to 10 clinical parameters through non‐invasive sensors attached to the skin. The measurements include 12‐lead ECG, Heart Rate, Heart Rate Variability, RR‐times, Respiration, Plethysmogram and Oxygen
Saturation.

Dyna‐Vision© automatically transmits cardiac events and even continuous real‐time ECG recordings to a secured server. Besides using a computer or laptop, physicians can now also monitor a patient’s real‐time vital signs on a G1 Android mobile phone. Physicians can use the application at anytime from anywhere around the world.

The Dyna-Vision G1 Telemedicine Application can only be used by licensed physicians after registration with RS TechMedic B.V.

On Thursday, Google and IBM will unveil a new initiative that will allow Google Health, a site where users can store and track information about their medical history, to connect to and stream data from medical devices. In demonstrations, IBM and Google fitted Wi-Fi radios to gadgets like heart rate monitors, blood pressure cuffs, scales and blood-sugar measurement meters, allowing the devices to communicate with a PC and feed real-time medical information directly into Google’s online records.

Hooking up those devices to the Web, IBM argues, will offer a new immediacy and granularity of health monitoring. A user can remotely track the blood pressure readings or glucose levels of a diabetic parent living alone, or stream his or her medical information like weight or heart rate directly to a doctor or physical trainer.

“If there’s something abnormal, you can catch it before you have an episodic intervention, like going to the emergency room,” says Dan Pelino, manager of IBM’s health care division. “This is like OnStar for a patient, keeping constant information about you and sending alerts even before you have a problem.”

More on Google Health on Pimm:

Meet Dr. Google Health: Roni Zeiger, right from Stanford!

Google Factory Tour of Health: watch the pivotal moment!

FriendFeed comments: The hidden backyard

Late Google Health: catching up with the past, first!

A bit of history: The official launch of Google Health, 19/05/08

By making inquiries with local surplus brokers, Rienhoff discovered he could buy a secondhand PCR machine for less than a MacBook. He ended up purchasing a full working model for just $750.
Obtaining additional supplies, like the PCR reagents, for his experiment was tougher. Some chemical companies didn’t want to ship to a private address, so Rienhoff pretended his house was the headquarters of the fictional Institute for Future Study.

While Rienhoff could spring for his own PCR machine, a used gene sequencer (assuming he could find one) would cost around $100,000. So he found a university lab (which he declines to identify) that would sequence the genes he had amplified, for $3.50 per 50-microliter sample. In spring 2007, Rienhoff mailed in more than 200 samples.

Rienhoff compared Beatrice’s DNA with the information on Ensembl, looking for any base-pair variants that hadn’t been previously recorded on Ensembl. He was operating on the assumption that Beatrice’s genetic blip was completely unknown, which would explain why she’d been so hard to diagnose. The job was daunting: The printouts contained data for approximately 20,000 base pairs, and there was no feasible way to automate the hunt for variants. After putting in a full day of consulting and then getting the kids to bed, Rienhoff would retire to his attic and spend hours checking Beatrice’s adenines (A), thymines (T), guanines (G), and cytosines (C) against the Ensembl reference genome.

]]> http://pimm.wordpress.com/2009/01/29/practical-dna-hugh-rienhoffs-got-a-story-to-tell/feed/ 8 attilachordash http://pimm.wordpress.com/2009/01/15/bioblocks-outsourcing-biotech-one-block-at-a-time/ http://pimm.wordpress.com/2009/01/15/bioblocks-outsourcing-biotech-one-block-at-a-time/#comments Thu, 15 Jan 2009 17:53:33 +0000 attilachordash http://pimm.wordpress.com/?p=2356 ]]> Friend Dan Erlanson (Co-Editor in Chief of the niche and smart Fragment-based Drug Design blog Practical Fragments) sent me this story on the recession proof business model of a biotech company called BioBlocks and his founder medical chemist Peter Pallai:

Approximately one out of 5,000 compounds pass an initial screen, hit the designated biological target, and end up making it to clinical trials. So Pallai’s pitch is simple. He and his team are good at one thing-chemical synthesis of new drug candidates to hit those targets. By outsourcing this piece of the puzzle to his team of chemists, about 25 of whom work in Budapest, Hungary, biotech companies can get the work done fast and well, he says. It makes sense professionally for his chemists as well, because they can get steady work, rather than hitch their wagons to one of hundreds of biotechs that dream of becoming the next Genentech, but are more likely to end up flaming out in a few years.

from my mailbox:

We are shortly to publicly announce the first UK Maker Faire but thought you would appreciate advanced notification.
The Make team forwarded me your names and email addresses as they believe you might be interested in the Newcastle upon Tyne Maker Fair on March 14th-15th 2009.

The first UK Maker Fair will take place in Newcastle 14-15 March as part
of Newcastle ScienceFest – a 10 day festival celebrating creativity and
innovation.

This two-day, family-friendly event celebrates the Do-It-Yourself (DIY) mindset and features interactive exhibits organized by individual enthusiasts, hobbyist groups and clubs as well as student groups. It’s for creative, resourceful folks who like to tinker and love to make things. Maker Faire is an opportunity to share what you do with others.

Are you interested in joining us in Newcastle and showing off your latest exhibits?
Please let us know and we will forward you details as they become available.

I would appreciate if you could send me a list of your fellow makers that you think would appreciate this advanced notification.

I am looking forward to hearing from you.
Kindest regards
Josette
###
Josette Garcia
O’Reilly UK Limited
www.oreilly.com

The book is to be called The Decision Tree (explanation below) accompanied by a new website. Thomas is the perfect man for this job, he is the deputy editor of Wired magazine (=he is well informed and connected), a good journalist who took his job (writing on science, health and medicine) so seriously that he went back to school to get a degree in Public Health. Back in the days his very early coverage on 23andMe (actually published before the official launch of the service) was actually the only serious insight on 23andMe.

With this book Thomas will have a chance to become the Chris Anderson or Malcolm Gladwell of personalized medicine and public health.

“The premise is that we are at a new phase of health and medical care, where more decisions are being made by individuals on their own behalf, rather than by physicians, and that, furthermore, these decisions are being informed by new tools based on statistics, data, and predictions. This is a good thing – it will let us, the general public, live better, happier, and even longer lives. But it will require us to be stewards of our health in ways we may not be prepared for. We will act on the basis of risk factors and predictive scores, rather than on conventional wisdom and doctors recommendations. We will act in collaboration with others, drawing on collective experience with health and disease, rather than in the isolation and ignorance that can come with “privacy” concerns. And we will act early, well before symptoms appear, opting to tap the science of genomics and proteomics in order to mitigate our risks down the road.

Together, these tools will create a new opportunity and a new responsibility for people to act – to make health decisions well before they become patients. This can be characterized as a decision tree, a series of informed choices we will make to minimize uncertainty and optimize our outcomes. Indeed, we will use decision trees to navigate most of our health decisions, sometimes in overt ways – new decision support tools will both inform us and guide us, and they’ll be steeped in statistics, prediction, and the power of collective experience.”

and here we go….Happy Holidays Grandma you’got a 2fold risk for psoriasis but don’t worry too much about the Alcohol Flush Reaction and your caffeine consumption!

Actually I tried to convince Anna and my mom, also other relatives to enter the field of personal genomics and give me 2 mls of spits…so 3 kits would cost me circa 1000 bucks plus 3x$70 Fedex damage (no combined Fedex package for 3 kits?)…and how many dollars do I have? Oh, I think that’s private and hope Anna won’t read this post too.

But who will genotype Santa? And what about the singles? By the way, Christmas, here’s my video for you:

Tip: Genetic Future

How do you interpret the following situation: we have a life extension technologist whose all endeavors is about pushing this issue to its very limits and making things possible but on the other hand this very life extensionist himself is not driven by actually living as long as he can.

It seems that SENS theorist Aubrey de Grey, who is chronologically 45, (BioBarCamp photo by Ricardo) is taking roughly the above position in a recent interview. Aubrey is a good and witty interviewee and of course the interpretation of what he is saying is strongly context dependent so here is the full question and answer:

Question: One hundred years of life can wear you down physically, but it can also wear you down emotionally… perhaps even existentially. For you, is a desire to live long accompanied by a desire to live long in a much-improved human civilization, or is this one satisfactory?

Aubrey de Grey: I’m actually not mainly driven by a desire to live a long time. I accept that when I’m even a hundred years old, let alone older, I may have less enthusiasm for life than I have today. Therefore, what drives me is to put myself (with luck) and others (lots and lots of others) in a position to make that choice, rather than having the choice progressively ripped away from me or them by declining health. Whether the choice to live longer is actually made is not the point for me.

Let’s see 2 possible and extreme interpretations of this answer (neither of them is my own interpretation) and I hope my readers can find fine-tuned arguments in between while thinking a bit about this still rather philosophical topic:

1., Saying that we want the process (a robust healthy lifespan technology) but not necessarily the product (a robust healthy lifespan) of our own business is a disaster from a marketing point of view and has a withdrawal feeling that comes in handy for any kind of anti-life extension position. It’s Steve Jobs using a Windows PC instead of a Mac and an Android G1 instead of an iPhone. Or simply it is Aubrey saying no to a would-be personal MitoSENS somatic gene therapy putting backup copies of Aubrey’s own vulnerable mitochondrial genes into the nuclei later on in order to live a longer life.

2., It’s the only realistic position current day middle aged life extensionists can take: working to empower future generations to make that choice while it is utterly unrealistic that any substantial technological benefit will return to the current generation. From this angle the life extensionist activity can be interpreted as a noble altruist endeavor raising intergenerational justice by reducing the asymmetry in the relations of past and future generations.

Update: Aubrey was kind enough to answer my interpretative question in a detailed comment included here:

Neither of these interpretations is correct, not even close! My answer in that interview (which I have given in many other places too) is a true reflection of what I feel. Concerning (2), no, I think I do have a respectable chance of benefiting from rejuvenation technologies, especially since I’m signed up to be cryopreserved. Concerning (1), the product is not only the lifespan but the avoidance of frailty and disease, and that’s the main thing that drives me (which is convenient, because it is indeed easier to market).
But even if we presume complete success against frailty and disease, and we just look at lifespan per se, then I don’t see any problem with my position – either a logical problem or a marketing problem. I think there are valid reasons for wanting to live literally forever, particularly the philosophical view that one’s life is meaningless if one ever dies – but I don’t hold that view, or at least I don’t base my life around any concept of the meaning of life. Wanting to live as long as one can is something that can be motivated by, for example, having things one wants to do that may take an extremely long time, such as visiting extrasolar planets – but I don’t have any such desire. One might want to avoid dying for social reasons, such as preventing the suffering of one’s loved ones who will be bereaved, but that’s not much of a reason in my view. Then there is the innate enjoyability of life, the fact that certain activities provide immediate pleasure – but death removes the
motivation to plan for future gratification, so “living for the moment” doesn’t seem to motivate living longer than the specific moments that one is already anticipating. So, what does that leave? – only a desire to live long enough to fulfil one’s current goals, plus an expectation that one will continue to acquire new goals. But an expectation of future desires is not the same as a present desire, because the expectation may not be borne out: it’s only an argument for forward planning. And that’s all I was saying.

Resource link/Story suggestion for your website:Title: VADLO – Biomedical Search Engine
Description: Vadlo is a search engine for the biology/biomedical scientists, educators, clinicians and reference librarians.
References
Also check the Daily cartoons!

The idea is that we feed them with searches and links and they will grow big enough to give us more and more relevant searches and links. Magic concept: scalability, check the motivation behind the name choice:

Vadlo: (vud-lo) – Vadlo is a large fig tree characterized by aerial roots that eventually become accessory trunks. This allows it to grow horizontally to amazing proportions.

I find the 5 basic search categories amazing and after a short tinkering it can already throw out interesting sources:

From the about page:

Protocols category will let you search for methods, techniques, assays, procedures, reagent recipes, plasmid maps, etc. Online Tools will cater calculators, servers, prediction tools, sequence alignment and manipulation tools, primer design etc. Seminars are essentially powerpoint files for presentations, lectures and talks. Databases will take you to, well, databases, resources, compilations, lists etc. It is here that you can also search for your favorite genes and proteins. Software category is for bioinformatics experts who are looking for codes, scripts, algorithms, executables, downloadable programs and collaborations. Please realize this is beta, or pre-beta, if you prefer. Vadlo index is expanding everyday and your favorite link/s will be indexed pretty soon.