Guest Post: The one billion map

Image courtesy of Albert-László Barabási.

Image cour­tesy of Albert-​​László Barabási.

Ear­lier this month, the Obama admin­is­tra­tion announced its plan to put $100 mil­lion toward building a net­work map of the human brain. World leading net­work sci­en­tist and North­eastern Dis­tin­guished Pro­fessor Albert-​​László Barabási is excited about the new project, but says the so-​​called “con­nec­tome” of neural inter­ac­tions in the brain is but one net­work of many deserving more atten­tion and funding. Here he dis­cusses the net­work of mol­e­c­ular inter­ac­tions in the body that define and deter­mine dis­ease. This post was orig­i­nally pub­lished on the  Face­book page for Network Sci­ence: Inter­ac­tive Text­book, a project of Barabási and his col­leagues at the Center for Com­plex Net­work Research.

For a net­work sci­en­tist few things can be more exciting that when the US gov­ern­ment com­mits $100 mil­lion a year for its most mas­sive net­work map­ping ini­tia­tive ever: obtain a map of the con­nec­tome, a com­plete cir­cuitry of the brain. The effort’s scale and com­plexity only com­pares to Google’s mighty oper­a­tion to map out the WWW and Facebook’s ambi­tion to map out the world’s social cir­cuitry. Yet, it also reminds us of our biggest map-​​making chal­lenge to date: the lack of a map of the inter­ac­tome, rep­re­senting the full list of mol­e­c­ular inter­ac­tions between the genes in a human cell. The absence of this map remains the major bar­rier between the $3 bil­lion invest­ment into genomics and our ability to cure human disease.

A car with dys­func­tional lights has many sim­i­lar­i­ties to a human with a dis­ease. There is one dif­fer­ence, how­ever: if we get the car to a mechanic, we are cer­tain that he will be able to fix it. Why can the mechanic, with far less edu­ca­tion than a doctor, guar­antee to fix our car, while many human dis­eases remain untreated? To begin with, the mechanic has the com­plete parts list. Well, so does the doctor: the Human Genome Project offered for the first time the full inven­tory of the cell’s com­po­nents, a com­pre­hen­sive list of genes, pro­teins and RNAs. We fully expected that this parts list would result in a bonanza of new drugs and treat­ments. It did not. In 2000, the year before the human genome was unveiled, the FDA approved over a hun­dred drugs. This number fell to about twenty a year a decade later.

In hind­sight, your car’s parts list is not suf­fi­cient to fix your lights either. The mechanic also needs the car’s wiring dia­gram, telling him to check the bat­tery, the fuses, and the switches, to look for loose cables instead of checking the tire pres­sure. Sim­i­larly, if we ever want to develop new drugs and cure dis­ease, we need a detailed map, telling us how our genes and pro­teins work together. Indeed, count­less studies have shown that knowing the genes mutated in cancer, asthma, or schiz­o­phrenia is insuf­fi­cient to under­stand and cure the dis­ease. These are true net­works dis­eases: the fail­ures of the com­po­nents make sense only in the con­text of the net­works in which they participate.

The chal­lenge of the con­nec­tome and the inter­ac­tome cannot be more dif­ferent. The goal of the unveiled con­nec­tome ini­tia­tive is to develop the tech­nolo­gies that one day will help us map the brain. In con­trast, the tools to map the inter­ac­tome are largely avail­able. For example, during the last decade Marc Vidal, a geneti­cist from the Dana Farber Cancer Insti­tute and many others have tire­lessly improved the tools to map all binding inter­ac­tions between the pro­teins of a human cell. Col­lab­o­rating with Vidal, in 2007 we esti­mated that the maps avail­able back then were about 5% com­plete. This year they are about to reach a land­mark: a map that con­tains 20% of the links. How­ever, that also means that we are still missing 80% of the inter­ac­tions. Imagine that your mechanic’s blue­print would lack 80% of the car’s internal circuitry—would you ever dare to take your car to him?

Per­haps the most pro­found dis­covery of net­work sci­ence is that fun­da­men­tally dif­ferent net­works, such as the WWW, the cell, or the social net­work, are gov­erned by sim­ilar laws and have a common blue­print. How about the brain? Do hubs, like Google is on the WWW or the P53 pro­tein is in the human cell, dom­i­nate its archi­tec­ture? Do nodes form tightly linked com­mu­ni­ties, as humans do in the social net­work? Is our brain a small world? Lacking brain maps, we have no idea. The human brain is truly terra incog­nita from the net­work per­spec­tive. The con­nec­tome aims to change that, offering hope that one day we will have the tools to uncover the brain’s fun­da­mental pat­terns of con­nec­tivity. In the case of the inter­ac­tome we have the tools to map it out. What the research com­mu­nity lacks is the will and the resources to see it to the end. And while we can only imagine the ben­e­fits of the con­nec­tome, we know exactly what we loose by not pur­suing the inter­ac­tome: we are let­ting a $3 bil­lion invest­ment into genomics unex­ploited. And with that, count­less dis­eases remain untreated.