New math brings machine learning to the next level

A team of Italian mathematicians, including one who is also a neuroscientist from the Champalimaud Centre for the Unknown (CCU), in Lisbon, Portugal, has shown that artificial vision machines can learn to recognize complex images spectacularly faster by using a mathematical theory that was developed 25 years ago by one of this new study's co-authors. Their results have been published in the journal Nature Machine Intelligence.

During the last decades, machine vision performance has exploded. For example, these artificial systems can now learn to recognizeCAPTION The new approach allows artificial intelligence to learn to recognize transformed images much faster.  CREDIT Diogo Matias virtually any human face - or to identify any individual fish moving in a tank, in the midst of a large number of other almost identical fish which are also moving. {module In-article}

The machines we're talking about are, in fact, electronic models of networks of biological neurons, and their aim is to simulate the functioning of our brain, which is as good as it gets at performing these visual tasks - and this, without any conscious effort on our part. 

But how do these neural networks actually learn? In the case of face recognition, for instance, they do it by acquiring experience about what human faces look like in the form of a series of portraits. More specifically, after being digitized into a matrix of pixel values (think about your computer monitor's RGB system), each image is "crunched" inside the neural network, which then manages to extract general, meaningful features, from the set of sample faces (such as the eyes, mouth, nose, etc).

This learning (deep learning, in its more modern development) then enables the machine to spit out another set of values, which will in turn enable it, for instance, to identify a face it has never seen before in a databank of faces (much like a fingerprint database), and therefore to predict who that face belongs to with great accuracy.

The story of Clever Hans

But, before the neural network can begin to perform this well, though, it is typically necessary to present it with thousands of faces (i.e. matrices of numbers). Moreover, much as these machines have been increasingly successful at pattern recognition, the fact is that nobody really knows what goes on inside them as they learn their task. They are, basically, black boxes. You feed them something, they spit out something, and if you designed your electronic circuits properly... you'll get the correct answer.

What this means is that it is not possible to determine which or how many features the machine is actually extracting from the initial data - and not even how many of those features are really meaningful for face recognition. "To illustrate this, consider the paradigm of the wise horse", says the first author of the study Mattia Bergomi, who works in the Systems Neuroscience Lab at the CCU.

The story dates from the early years of the 20th century. It's about a horse in Germany called Clever Hans that, so his master claimed, had learned to do arithmetics and announce the result of additions, subtractions, etc. by tapping one of its front hooves on the ground the right number of times. Everyone who witnessed the horse's performance was convinced he could count (the event was even reported by the New York Times). But then, in 1907, a German psychologist showed that the horse was, in fact, picking up unconscious cues in his master's body language that were telling it when to stop tapping...

"It's the same with machine learning; there is no control over how it works or what it has learned during training", Bergomi explains. The machine having no a priori knowledge of faces, it just somehow does its stuff - and it works.

This led the researchers to ask: could there be a way to inject some knowledge of the real world (about faces or other objects) into the neural network, before training, in order to cause it explores a more limited space of possible features instead of considering them all - including those that are impossible in the real world? "We wanted to control the space of learned features", Bergomi points out. "It's similar to the difference between a mediocre chess player and an expert: the first sees all possible moves, while the latter only sees the good ones", he adds.

Another way of putting it, he says, is by saying that "our study addresses the following simple question: When we train a deep neural network to distinguish road signs, how can we tell the network that its job will be much easier if it only has to care about simple geometrical shapes such as circles and triangles?".

The scientists reasoned that this approach would substantially reduce training time - and, not less importantly, give them a "whiff" of what the machine might be doing to obtain its results. "Allowing humans to drive the learning process of learning machines is fundamental to move towards a more intelligible artificial intelligence and reduce the skyrocketing cost in time and resources that current neural networks require in order to be trained", he remarks.

What's in a shape? {module In-article}

Here's where a very abstract and novel mathematical theory, called "topological data analysis" (TDA), enters the stage. The first steps in the development of TDA were taken in 1992 by the italian mathematician Patrizio Frosini, co-author of the new study and currently at the University of Bologna. "Topology is one of the purest forms of math", says Bergomi. "And until recently, people thought that Topology would not be applied to anything concrete for a long time. Until TDA became famous in the last few years."

Topology is a sort of extended geometry that, instead of measuring lines and angles in rigid shapes (such as triangles, squares, cones, etc.), seeks to classify highly complex objects according to their shape. For a topologist, for example, a donut and a mug are the same objects: one can be deformed into the other by stretching or compression.

Now, the thing is, current neural networks are not good at topology. For instance, they do not recognize rotated objects. To them, the same object will look completely different every time it is rotated. That is precisely why the only solution is to make these networks "memorize" each configuration separately - by the thousands. And it is precisely what the authors were planning to avoid by using TDA.

Think of TDA as being a mathematical tool for finding meaningful internal structure (topological features), in any complex "object" that can be represented as a huge set of numbers, by looking at the data through certain well-chosen "lenses" or filters. The data itself can be about faces, financial transactions or cancer survival rates. For faces in particular, by applying TDA, it becomes possible to teach a neural network to recognize faces without having to present it with each of the different orientations faces might assume in space. The machine will now recognize all faces as being a face, even in different rotated positions.

It's 5! No, it's a 7!

In their study, the scientists tested the benefits of combining machine learning and TDA by teaching a neural network to recognize hand-written digits. The results speak for themselves.

As these networks are bad topologists and handwriting can be very ambiguous, two different hand-written digits may prove indistinguishable for current machines - and conversely, two instances of the same hand-written digit may be seen by them as different.

That is why, to be performed by today's vision machines, this task requires presenting the network, which knows nothing about digits in the world, with thousands of images of each of the 10 digits, written with all sorts of slants, calligraphies, etc..

To inject knowledge about digits, the team built a set of a priori features that they considered meaningful (in other words, a set of "lenses" through which the network would "see" the digits), and forced the machine to choose among these lenses to look at the images. And what happened was that the number of images (that is, the time) needed for the TDA-enhanced neural network to learn to distinguish 5's from 7's - however badly written -, while maintaining its predictive power, dropped down to less than 50! "What we mathematically describe in our study is how to enforce certain symmetries, and this provides a strategy to build machine learning agents that are able to learn salient features from a few examples, by taking advantage of the knowledge injected as constraints", says Bergomi.

Does this mean that the inner workings of learning machines which mimic the brain will become more transparent in the future, enabling new insights on the inner workings of the brain itself? In any case, this is one of Bergomi's goals. "The intelligibility of artificial intelligence is necessary for its interaction and integration with biological intelligence", he says. He is currently working, in collaboration with his colleague Pietro Vertechi, also from the Systems Neuroscience Lab at CCU, on developing a new kind of neural network architecture that will allow humans to swiftly inject high-level knowledge into these networks to control and speed up their training.

Columbia creates detailed map to show how viruses infect humans

Biologists at Columbia University Irving Medical Center have leveraged a computational method to map protein-protein interactions between all known human-infecting viruses and the cells they infect. The method, along with the data that is generated, has spawned a wealth of information toward improving our understanding of how viruses manipulate the cells that they infect and cause disease. Among its findings, the work uncovered a role for estrogen receptor in regulating Zika Virus (ZIKV) infection, as well as links between cancer and the human papillomavirus (HPV).

The research, led by Sagi Shapira, Ph.D., Assistant Professor in the Department of Systems Biology and the Department of Microbiology & Immunology at Columbia University Vagelos College of Physicians and Surgeons, appears today in the journal, Cell. Dr. Shapira’s collaborators include Professors Barry Honig, Ph.D., of Systems Biology and of Biochemistry and Molecular Biophysics and Raul Rabadan, Ph.D., of Systems Biology and of Bioinformatics. Researchers implement P-HIPSTer, an in silico computational framework that leverages protein structure information to identify approximately 282,000 protein-protein interactions across all fully-sequenced human-infecting viruses (1001 in all). This image highlights that in addition to rediscovering known biology, P-HIPSTer has yielded a series of new findings and enables discovery of a previously unappreciated universe of cellular circuits and biological principles that act on human-infecting viruses. (Image Courtesy of Dr. Sagi Shapira)

From seasonal influenza and chickenpox, which are largely treatable, to life-threatening emerging viruses, such as Ebola and Zika, infections can result in a wide range of clinical symptoms and outcomes. At the molecular level, viruses invade cells and manipulate them to replicate, survive, and cause disease. Since they depend on human cells for their life cycle, one-way viruses co-opt cellular machinery is through protein-protein interactions within their cell host. Similarly, cells respond to infection by initiating immune responses that control and limit viral replication – these too, depend on protein-protein interactions. {module In-article}

To date, considerable effort has been invested in identifying these key interactions – and many of these efforts have resulted in many fundamental discoveries, some with therapeutic implications. However, limitations on scalability, efficiency, and even access have limited the use of traditional methods. To address this challenge, Dr. Shapira and his collaborators developed and implemented a computational framework, termed P-HIPSTER, that infers interactions between pathogen and human proteins, the building blocks of viruses and cells. 

Until now, our knowledge about many viruses that infect people is limited to their genome sequences. Yet, for most viruses little has been uncovered about the underlying biological interactions that drive these relationships and give rise to disease. 

“There are over 1,000 unique viruses that are known to infect people,” says Dr. Shapira. “Yet, despite their unquestionable public health importance, we know virtually nothing about the vast majority of them. We just know they infect human cells. The idea behind this effort was to systematically catalog the interactions that viruses have with the cells they infect. And, by doing so, also reveal some really interesting biology and provide the scientific community with a resource that they can use to make interesting observations of their own.” 

Based on the PrePPI algorithm (developed in Professor Honig’s Laboratory), P-HIPSTer exploits protein structural information to systematically interrogate virus-human protein-protein interactions with remarkable accuracy. Dr. Shapira and his collaborators applied P-HIPSTer to all 1,001 human-infecting viruses and the approximately 13,000 proteins they encode. The algorithm predicted roughly 280,000 likely pairs of interacting proteins that represent a comprehensive catalog of human virus protein-protein interactions with an accuracy rate of almost 80 percent.

“This is the first step towards building comprehensive cartography of physical interactions between different organisms,” Dr. Shapira says. 

Series of New Findings: Zika, HPV, Viral Evolution

In addition to defining pan-viral protein interactions, P-HIPSTer has yielded new biological insights into the Zika virus, HPV, and the impact of viruses in shaping human genetics. 

Among their discoveries, the researchers found that Zika virus interacts with the estrogen receptor, the protein that allows cells to effectively respond to the estrogen hormone. Importantly, they found estrogen receptor has the potential to inhibit Zika virus replication. Says Dr. Shapira, “And, in fact, estrogen receptor inhibits viral replication even more than interferon, a protein that is the body’s first line of defense to viral infection and our gold standard for anti-viral defense.”

The finding is particularly relevant to clinical disease as pregnant women are most susceptible to Zika during their first trimester, which is when estrogen levels are at their lowest. This period also is when the fetus is most susceptible to Zika, a virus for which there is no vaccine or specific treatment and that can cause severe birth defects.

Dr. Shapira and his team also explored interactions between human papillomavirus (HPV; the leading cause of cervical cancer) and the cells that it infects. HPV is the most common sexually transmitted infection with approximately 80 percent of sexually active individuals contracting one of the 200 different types of HPV at some point in their lives.  Dr. Shapira and his team used the data generated by P-HIPSTer to identify protein-protein interactions that distinguish HPV infections associated with cancer from those that are not. In addition to providing insights into how HPV may cause disease, the finding could lead to improved diagnostics for those infected with HPV, and P-HIPSTer could potentially be used to help predict whether or not any particular virus is likely to be highly pathogenic. 

The researchers also examined whether the interactions mediated by viruses have impacted human genetics. The researchers found evidence of strong selection pressure for several dozen cellular proteins have been shaped by a viral infection, unlocking new insights into how our genome has been impacted by viruses. 

“One of the things we can do with this data is drilled down and ask whether virus infection has changed the history of human genetics,” notes Dr. Shapira. “That is certainly not a novel idea but to have a catalog of what those proteins are is significant. There are a lot of areas that we can explore now that we couldn’t before.” 

Future Work

Dr. Shapira and his team intend to apply P-HIPSTer on more complex pathogens, such as parasites and bacteria and use it to better understand how bacteria in the human gut communicate with each other. In the future, the algorithm could also be used to explore viruses or pathogens that affect agricultural plants or livestock. 

The Shapira Laboratory at Columbia University is working to decipher the genetic and molecular circuitry at the interface of host-pathogen interactions. A deeper understanding of these relationships provides important insights into cellular machinery that control basic cell biology and has broad implications in human translational immunology and infectious disease research.

The paper, “ A Structure-Informed Atlas of Human-Virus Interactions ”, is also co-authored by: Gorka Lasso (Columbia Systems Biology and Microbiology & Immunology); Sandra V. Mayer (Columbia Systems Biology and Microbiology & Immunology); Evandro R. Winkelmann (Columbia Systems Biology and Microbiology & Immunology); Tim Chu (Columbia Systems Biology); Oliver Elliot (Columbia System Biology); Juan Angel Patino-Galindo (Columbia Systems Biology); and Kernyu Park (Columbia Biomedical Informatics).

P-HIPSTer derived interactions can be accessed via http://phipster.org. The study’s results are available through an interactive web server that enables both searchable queries and data download. 

Russian scientists create new model of heat transfer in crystals for development of next generation supercomputers

Russian scientists suggested a model describe the distribution of heat in ultrapure crystals at the atomic level

Today's physicists mostly focus either on massive objects like black holes or on atom-sized objects. In both cases, significant deviations from conventional laws of physics are observed. The understanding of atomic-level processes opens a wide range of prospects in nanoelectronics and material engineering. One of such studies is a model suggested by a team of scientists from Peter the Great St.Petersburg Polytechnic University (SPbPU). The model describes the distribution of heat in ultrapure crystals at the atomic level. The article was published in the Journal of Applied Mathematics and Mechanics.

The distribution of heat in nanostructures is not regulated by the laws applied to conventional materials. This effect is most vividly expressed in the reaction between graphene and a laser-generated heat point source. Graphene is a 2D crystal made of carbon atoms. The material looks like a thin grid or a honeycomb. However, it is quite stable and has very high heat and electrical conductivity due to which it is widely used in electrical engineering. The discoverers of this unique crystal were awarded the Nobel Prize in Physics in 2010.

Scientists of SPbPU considered an infinite crystal consisting of identical particles obeying classical Newtonian equations of motion. Graphene-based technologies are rarely used in a vacuum, so the team also took into account the effect of the environment (gas or liquid). This adjustment has a considerable impact on the model as a part of the heat is spent on warming up the environment. Finally, the team derived an analytical solution describing heat transfer. To describe the processes that happen in the material, the scientists obtained simple equations and confirmed them with numerical data generated in the model for different distances from the heat source. Using the developed model, the team observed that a crystal have certain directions along which the heat rays distribute the major part of energy. Currently, the authors are preparing for an experiment to confirm their theoretical conclusions with actual heat processes in a graphene crystal.

"Our results may be widely used for investigation of heat transfer in micro- and nano processors. It is of great importance for the development of new generation high-performance computers. Our analytical approach can be applied to a wide range of ultrapure materials such as graphene", concluded Anton KRIVTSOV, corresponding member of the Russian Academy of Sciences, the Head of the Higher School "Theoretical Mechanics", Director of Research & Education Center "Gaspromneft-Polytech" at Peter the Great St. Petersburg Polytechnic University.