################# ¶
Deciphering Aging ¶
################# ¶
:Abstract: Denigma is a Digital Decipher Machine that can encode and decode data in the web. It is specifically devoted to decipher the aging process by utilizing and systematizing the rapidly increasing amount of available biological data and any other information with relevance to aging research. Denigma structures the informatiothe n in form of facts and enables modular access to diverse data and logical reasoning on the constructed knowledge base. This enables decoderly alogorithms to do global inference and pning on web-scale and therefore the identification of high effective interventions by considering all previous knowledge and making high-confidence testable predictions. ¶
¶
Introduction ¶
============ ¶
.. Denigma is a Manhatten-Project like endeavour of the International Longevity Alliance (ILA) and is its major information technological flagship which is automating the discovery of novel therapeutics that will be tested in a by the ILA proposed testing center [Figure: Roadmap Concept]. ¶
¶
Denigma is a project of the International Longevity Alliance and functions as its main information technological platform. One of its aims is to automate the discovery of novel therapeutics to be tested [Figure: The Vision]. ¶
¶
.. figure:: http://dgallery.s3.amazonaws.com/roadmap_concept.svg &para]
¶
Figure: The Vision ¶
¶
The construct of a digital decipher machine will allow the creation of a web intelligence capable of reverse-engineering the aging process within our lifetime. ¶
¶
Specifically Denigma uses advanced information technologies such as semantic web and machine learning bundled with information theory and combined with crowdsourcing for longevity research. Its development is lead by a group of enthusiasts which consists of scientists researching aging and engineers from software development industry as well as social networkers. ¶
¶
Data Unification ¶
================ ¶
The semantic web is an extension of the current world wide web in which meaning is added to the individual information pieces contained in web documents. In its core information is represented in form of triples which are making up the Resource Description Description, a universal language to represent knowledge [Figure: Semantic Web Stack]. Denigma leaverages semantic web technologies and builds on top of it. ¶
¶
.. figure:: http://dgallery.s3.amazonaws.com/semantic_web_technology_stack.png &para]
¶
Figure: Semantic Web Stack. ¶
¶
Specifically Denigma invents a novel form the semantic network based on Data Units that is compatible with the existing technologies and is even more flexible [Figure: Data Units]. ¶
¶
.. figure:: http://dgallery.s3.amazonaws.com/data_app.png &para]
¶
Figure: Data Units. ¶
¶
A key technology of the required integration of heterogneous data on aging are ontologies, which are like a schema for data and used extensively not only in the semantic web, but also software development and artifical intellegence. Denigma takes advantage of the existing technologies and generates missing and complementing ontologies such as those required for describing the aging process and integration and analysis of heterogenous biological networks [Figure: Ontology Visualization]. ¶
¶
.. figure:: http://dgallery.s3.amazonaws.com/ontology_development.png &para]
¶
Figure Ontology Development. ¶
¶
Enhancing Aging Research ¶
======================== ¶
Denigma functions also as a communication device that establishes and maintenance of collaborations under the linking researcher project and the world-wide continous longevity meeting. ¶
¶
Overall Denigma establishes an information technology (IT) ecosystem that speeds up anti-aging research and activism, summarizes collected knowledge and infers new knowledge from collected one. ¶
¶
So far Denigma already gathered a tremendous amount of facts about aging research. At the center is the lifespan application which systematizes all data from lifespan studies, over intervention to the individual factors that limit our lifespan. With Denigma it is easily possible to see what has already been achieved in anti-aging experiments and which factors influence aging. Further functional genomics information are utilized such as gene expression activity changes and interactions between biological entities to infer new possible factors with the power to tremendously extend the lifespan. ¶
¶
We are in strongly collaboration with famous aging reasearchers such as Joao Pedro de Magalhaes, the pionier of the genomics of aging and application of systems biology to understand aging, and Aubrey de Grey, the pionier of tackling aging as an enginering problem and the utilization of regenerative medicine to reverse aging, among many others. We recently started the construction of the worlds most comprehensive database on the genetic variants associated with longevity in humans, which will help computer-aided targeted drug discover to extend human healthspan. Further we are developing novel ways of making the aging process visually more attractive therefore also to attract citizen scientists and utilize the power of the crowd to complement automated algorithms to knowledge base creation as well as educate the public about aging as a problem [Figure: Lifespan Charts]. ¶
¶
.. figure:: http://dgallery.s3.amazonaws.com/lifespan_charts.png &para]
¶
Figure: Lifespan Charts. ¶
¶
There are numerous other applications developed on Denigma that are valuable for aging research, such as an management system that harbours information about experts researching on aging, transhumanists in general and activists as well as functionalities to enable real-time collaborations. Specifically we develop collaborative features to ease collaboration for researchers and activists. ¶
¶
In fact information technology is a field where a group of several developers working full-time can change a lot as features that we develop increase productivity of many of people involved in the field. And as for any IT platform all features of Denigma can also be used in many other fields (both research and not) that provides some extra opportunities. ¶
¶
* "Denigma for other fields": a lot of things that we do for aging are applicable and can be reused for other fields ¶
* knowledge management platform. Current knowledge management platforms (like semantic wiki) that are used by corporations and academia were developed too much time ago and do not meet the challenges of today so the features that we develop for aging researchers and activists will work there also ¶
* community possibilities. Lifespan-extensionist communities can be utilized to ¶
* educational opportunities. We develop graphs and ways of visualizations as well as quests that in combination with other features can be easily used for education purposes anywhere. ¶
* crowdsourcing for research. We are working on features that let researchers outsource parts of their work to volunteers. Projects like Aging genes project do well with this approach. ¶
* etc. When you create an ecosystem you often do not know beforehand what opportunities will it give you, but what is important here is that technologies/features together with user community that uses them. It always provide some new opportunities that are not known beforehand. Denigma is open-source that makes it easier to grow and attract new people. In the same time it is possible to provide some payed services and consultancy on top of open-source Denigma platform ¶
¶
Finding Anti-Aging Interventions ¶
================================ ¶
Computational methods developed on Denigma enable to identify effective therapeutics. Novel interventions can be found be utilizing top-down approache via the use of high-throughput omics data or bottom up via targeted approaches: ¶
¶
* Gene expression pattern matching ¶
* Network-based disssection ¶
* Computer-aided drug discover ¶
* Fact-based reasoning with ontologies ¶
¶
Gene Expression Pattern Matching ¶
-------------------------------- ¶
Gene expression activity patterns from transcriptomics data of already known lifespan extending interventions are used to derive common molecular signatures associated with longevity. Those signature are then matched with gene expression profiles of drugs that trigger similar gene expression patterns. Drugs that induce similar genes expression changes are with high accuarcy lifespan-extending drugs. Similiar meta -analysing aging-related gene expression changes is use to derive a common molecular signaure associated with aging. By comparing this signature with the gene expression profiles of drugs lets one identify those components that are reverse the age-related gene expression changes. Those drugs that revese agng gene expression changes are powerful anti-aging drugs capable of reversing aging. ¶
¶
Network-Base Dissection ¶
----------------------- ¶
Having a comprehensive inventory of all the factors that are associated with lifespan determination enables to apply network-approaches by utilizing interactomics data. For instance, given a list of the genes associated with a certain process like aging, one can apply the guilt-by-association concept which basically states that genes with more interactions than expected by chance with genes associated with a given process are likely to also play a role in that process, i.e. are potential drug targets. ¶
¶
Computer-Aided Drug Discovery ¶
----------------------------- ¶
By leverging distributed computing algorithms can identify drugs that fit exactly into the three-dimensional structure of the gene products of for example aging genes. ¶
¶
Fact-Based Reasoning with Ontologies ¶
------------------------------------- ¶
Logical reasoning of a consistence knowledge base with an apropriate designed ontologies allows to infer the causality of the chain of age-related changes and can suggest via revealing implicit hidden knowledge which therapies are most effective to reverse the those drivers of age-related changes. ¶
¶
Therefore, by utilizing such computational appraches Denigma will be able make recommendations on which experiments need to be done to gain greater insights about the mechanims of aging and how to reverse it as fast as possible by taking into account the current exsiting knowldge and data, as well as providing methods to estimate efficiency of potential life-extending interventions. ¶
¶
Conclusion ¶
========== ¶
Denigma is lies on the intersection of science, collaboration and machine learning [Figure: Denigma Concept]. It enhances scientific discoveries by combining both human intelligence via supporting collaborations and utilizing crowdsourcing with artifical intelligence by machine learning. ¶
¶
.. figure:: http://dgallery.s3.amazonaws.com/denigma.png &para]
¶
Figure: Denigma Concept. ¶
¶
¶
¶
Roadmap ¶
####### ¶
.. Anton: probably we should think about two documents, one the will explain roadmap in details, and one general (this one) with all possible directions ¶
¶
.. Daniel: All right, here is the Roadmap http://denigma.info/data/Roadmap/description &para]
¶
International Longevity Alliance vision and proposal ¶
---------------------------------------------------- ¶
Aging is very complex phenomena, and currying it is not an easy task. It is not a task for one researcher or a small group of researchers, in fact it is a matter of whole anti-aging community and even the whole society (as it is also a social issue). It is even much more important: Everyone ages, the anti-aging community alone is not sufficient to solve it. What we need is a revolution. ¶
¶
Understanding vs. repairing, ILA's approach (what is different from Aubrey's approach) ¶
-------------------------------------------------------------------------------------- ¶
To cure aging we need to decipher it first and then indentify and create treaments (interventions). Understanding all the mechanisms of aging and its causes is a hard task and thus it is always tepmting not to do it and limit ourselves to thinking of it as only damage-repair problem. ¶
¶
.. Should also provide hope at the same time ¶
¶
But the reality shows us that it does not work that way. There are numerous experiments starting from heterochronic parabiosis and organ replacement in old animals... [provide links and complete the phrase] that show us that the overall damaging processes in old organisms are very fast and just repairing does not work well, it is like patching up the holes in the dam. ¶
¶
.. He will probaly not know heterochronic parabiosis ¶
¶
Let us provide a simple analogy: not thinking about the causes of damages is good for cars because after you completely reparied an old rusty car you know that the pace of rusting will not be many times faster than for the new ones. So if it will break soon it should be something else that you simply forgot to repair. But experiments and studies show us that in old organisms it is different. In fact the regulation that is broken in aging organisms and we cannot fix it withough good understanding of aging process. ¶
¶
So solving aging is impossible withough understanding it. It would be nice but hard to understand it entirely. Meanwhile it will be already sufficient to understand it at the level that will let us slow down/reverse its processes in a way that will let us repair it faster than organism ages. ¶
¶
¶
Solving aging ¶
------------- ¶
Solving aging is not a simple task so we have some preferences but we can not say with absolute 100% certainty which of aging theories (or some entirely new one) is right. In fact the favourability of aging theories changes with new data and new assumptions. But what can do and what we are already doing is coordinating activities of anti-aging organisations and building an infrastructure that will tell them all (together with our own researchers) to work and collaborate more productively and solve aging much faster. ¶
¶
In order to decipher and then cure aging we need to: ¶
¶
* develop and improve our worlwide organization to attract people and resources and coordinate activities of all groups and individulas to solve aging. This is what is ILA all about ¶
* create an IT infrastructure for aging research because we need to summarize, analyse and collaborate on tones of data gathered and produced worldwide. It is what is Denigma all about ¶
* conduct experiments on various animals to test what we learned and to obtain new knowledge. That is a subject of "Testing Center" that is not yet established but is in our plans. ¶
¶
¶
"I have a plan" (Roadmap) ¶
------------------------- ¶
¶
TODO: integrate with Ilia's document: ¶
¶
Everything starts with planning, and each plan starts with some preliminary phase that involves styding of what exists, who are possible partners and what has been done so far. ¶
¶
Some information is already in our heads and in our portfolio but other needs some actions to be conducted and there are two approaches for this that can be combined: ¶
¶
¶
The first approach concludes in collecting needed info by making dedicated studies: ¶
¶
* conduct a survey and understand what is current state of affairs in anti-aging domain and related fields ¶
¶
* look at current state of affairs, choose the most effective technologies and ways to work and create our own strategy and action plan ¶
¶
* create a foresight of how it will be. The foresight includes not only our actions byt also our view of how others will act and how technologies will develop. And not only in aging field because aging researchers depend and are limited by worldwide state of technologies that will grow in future and there are also social issues that will influence funding ¶
¶
The main problem of the first approach is that it takes time and effort and thus money. The world is changing rapidly, so does the state of the art in aging research. So keeping it up to date needs conducting new studies that will need extra resources. ¶
¶
But of course it is not the only solution. ¶
¶
There is another, different way. ¶
¶
It relies on the fact that planing and information gathering is an iterative process: we need to learn in order to act and we can also learn by doing. So having a good IT infrastructure and beeing a hub of aging research and social activism let us obtain information constantly and minimizes a need for coducting determined studies because you will need just to take info from Denigma databases and do some small amount of extra work to produce them. So for the long term perspective second approach is better. ¶
¶
Planning and learning of what has been done in the field is not only a way to conduct our own planning, it also provides some opportunities: ¶
¶
* it easies advocacy for aging research and for seeking for investment opportunities ¶
¶
* with information and experties we will be able to provide the consultancy about the field help investors who are interested in projects in this area ¶
¶
* [TODO: add points] ¶
¶
¶
Deciphering Aging (Denigma) ¶
--------------------------- ¶
¶
Denigma is information technology (IT) ecosystem that speeds up anti-aging research and activism, summarizies collected knowledge and infers new knowledge from collected one. [todo: improve text and add links+pics] ¶
¶
We already gathered a tremendous amount of facts in our repositories and applications. At the center is the lifespan application which shows all the lifespan interventions and lifespan factors, so it is possible to see what has already been achieved in anti-aging experiments and which factors influence aging. Gene expressions, gene interactions and aging genes apps [picture of genes network] show aging from genetic points of view. ¶
¶
There are also other apps valuable for aging research. Now we are working hard on network analysis and semantic features that will allow us to automaticaly infer new knowledge out of existing. We also develop collaborative features to ease collaboration for researchers and activists. ¶
¶
In fact IT is a field where a group of several developers working fulltime can change a lot as features that we develop increase productivity of many of people involved in the field. And as for any IT platform all features of Denigma can also be used in many other fields (both research and not) that provides some extra opportunities ¶
¶
* "Denigma for other fields": a lot of things that we do for aging are applicable and can be reused for other fields ¶
¶
* knowledge managememnt platform. Current knowledge managemt platforms (like semantic wiki) that are used by corparations and academia were developed too much time ago and do not meet the challenges of today so the features that we develop for aging researchers and activists will work there also ¶
¶
* community possibilities. [todo: tell something how user communities are important and valiable] ¶
¶
* educational opportunities. We develop graph and other visualizations and quests that in combination with other features can be easily used for education purposes anywhere. ¶
¶
* crowdsourcing for the research. We are working on features that let researchers outsource parts of their work to volunteers. Projects like Aging genes project do well with this approach. ¶
¶
* etc. When you create an ecosystem you often do not know beforehands what opportunities will it give you. But what is important here is that technologies/features together with user community that uses them. It always provide some new opprotunities that are not known beforehand. Denigma is opensource that makes it easier to grow and attract new people. In the same time it is possible to provide some payed services and consultancy on top of opensource Denigma platform ¶
¶
[todo: add new points] ¶
¶
¶
Experimentations (Testing center) ¶
--------------------------------- ¶
¶
Having summarized and infered new knoledge we need to conduct experiments to test it and discover new facts. ¶
It is essential to have our own an aging research testing center for several reasons. ¶
¶
* We need to conduct a lot of lifespan experiments with many animals. Most of them share some common features that can be automized to make experiments cheaper and more reliable. Inside ILA there is AgeVivo project that managed to develop some new techniques for lifespan tests. ¶
* Different animal organizations (like PETA and others) are very successfull in lobbying prohibition of various animal experiments so researchers in such countries will be able to outsource those experiments that are prohibited to us. ¶
* We need to have a lot of old animals. Currently they are much more expensive in labs then young ones. There are also some species (like short-living apes) that is especially interesting for ageing interventions and we need to grow them cheaper ¶
¶
The testing center should not be one building in one city or country. It is possible to "go cloud". There are also a lot of small labs and volunteers that can help with experiments in many countries. With appropriate infrastructure it is possible to split experiments into different countries and collect/combine the results. It also makes it more reliable because if there are some errors in some labs (with treatment, statistics or puriness of mice lines) the results in others will show it up. ¶
¶
There are also some facilities and equipment that belong to ILA's activists that can be used: ¶
¶
* in Kyiv Immunology lab can freely use Kyiv Gerontology vivarium and owes some useful equipment (like two sequencers) ¶
* there are several DIY bio groups in Israel and France that are eager to collaborate ¶
¶
In the same time many challenges that aging researchers face (like legal regime) are same for many other fields that provides us some additional opportunities. Researchers and medical companies from other fields can be interested in ordering animal experiments. ¶
¶
.. Other stuff (not sure if we should mention it): consultancy on ageing related issues, ageing related medical diagnostics, DIY bio services for activists (to learn biology better), e ¶
¶
¶
Track record ¶
------------ ¶
should we tell about it?