Behavioral Neuroscience in the Era of Genomics: Tools and Lessons for Analyzing High-Dimensional Datasets

Behavioral neuroscience underwent a technology-driven revolution with the emergence of machine-vision and machine-learning technologies. These technological advances facilitated the generation of high-resolution, high-throughput capture and analysis of complex behaviors. Therefore, behavioral neuroscience is becoming a data-rich field. While behavioral researchers use advanced computational tools to analyze the resulting datasets, the search for robust and standardized analysis tools is still ongoing. At the same time, the field of genomics exploded with a plethora of technologies which enabled the generation of massive datasets. This growth of genomics data drove the emergence of powerful computational approaches to analyze these data. Here, we discuss the composition of a large behavioral dataset, and the differences and similarities between behavioral and genomics data. We then give examples of genomics-related tools that might be of use for behavioral analysis and discuss concepts that might emerge when considering the two fields together.     

Conductivity of a single DNA duplex bridging a carbon nanotube gap

We describe a general method to integrate DNA strands between single-walled carbon nanotube electrodes and to measure their electrical properties. We modified DNA sequences with amines on either the 5' terminus or both the 3' and 5' termini and coupled these to the single-walled carbon nanotube electrodes through amide linkages, enabling the electrical properties of complementary and mismatched strands to be measured. Well-matched duplex DNA in the gap between the electrodes exhibits a resistance on the order of 1 M(Omega). A single GT or CA mismatch in a DNA 15-mer increases the resistance of the duplex approximately 300-fold relative to a well-matched one. Certain DNA sequences oriented within this gap are substrates for Alu I, a blunt end restriction enzyme. This enzyme cuts the DNA and eliminates the conductive path, supporting the supposition that the DNA is in its native conformation when bridging the ends of the single-walled carbon nanotubes.     

The implementation of a 2-core, multi-threaded itanium family processor

The design of the high end server processor code named Montecito incorporated several ambitious goals requiring innovation. The most obvious being the incorporation of two legacy cores on-die and at the same time reducing power by 23%. This is an effective 325% increase in MIPS per watt which necessitated a holistic focus on power reduction and management. The next challenge in the implementation was to ensure robust and high frequency circuit operation in the 90-nm process generation which brings with it higher leakage and greater variability. Achieving this goal required new methodologies for design, a greatly improved and tunable clock system and a better understanding of our power grid behavior all of which required new circuits and capabilities. The final aspect of circuit design improvement involved the I/O design for our legacy multi-drop system bus. To properly feed the two high frequency cores with memory bandwidth we needed to ensure frequency headroom in the operation of the bus. This was achieved through several innovations in controllability and tuning of the I/O buffers which are discussed as well.     

Inhibition of expression of the lysine-rich 30 kDa surface antigen of Entamoeba dispar by the transcription of its antisense RNA

The gene coding for the 30 kDa lysine rich surface antigen (Ed-Ag) that is present on membrane surfaces of Entamoeba dispar trophozoites has been characterized. A specific monoclonal antibody MAb 318-28 prepared against this antigen reacts with all E. dispar strains tested, but not with any of the antigens of E. histolytica. In order to understand the function of this antigen, we constructed two plasmids, pEdA-9 and pEdA-Rev, in which the antigen-coding sequence was introduced into the pEhAct-Neo shuttle vector in the direct and opposite orientation, respectively. When E. dispar trophozoites were transfected with pEdA-9, only a slight increase was observed in the expression of the antigen. However, when E. dispar trophozoites were transfected with pEdA-Rev, the expression of the native 30 kDa antigen was significantly inhibited. This inhibition was proportional to the level of resistance of the E. dispar culture to the neomycin derivative G418. Cytopathic assays detected only a slight difference between untransfected, pEdA-9 transfected and pEdA-Rev transfected trophozoites.     

Fair attribution of functional contribution in artificial and biological networks

This letter presents the multi-perturbation Shapley value analysis (MSA), an axiomatic, scalable, and rigorous method for deducing causal function localization from multiple perturbations data. The MSA, based on fundamental concepts from game theory, accurately quantifies the contributions of network elements and their interactions, overcoming several shortcomings of previous function localization approaches. Its successful operation is demonstrated in both the analysis of a neurophysiological model and of reversible deactivation data. The MSA has a wide range of potential applications, including the analysis of reversible deactivation experiments, neuronal laser ablations, and transcranial magnetic stimulation "virtual lesions," as well as in providing insight into the inner workings of computational models of neurophysiological systems.     

Controlled analysis of neurocontrollers with informational lesioning

How does one aim to understand neural information processing? One of the difficult first challenges is to identify the roles of the network's elements. To this end a functional contribution analysis (FCA) method has been developed and applied for studying the neurocontrollers of evolutionary autonomous agents (EAAs). The FCA processes data composed of multiple lesion experiments and the corresponding performance levels that the agent obtains under these lesions. It calculates the contribution values (CVs) of the network's elements such that the ability to predict the agent's performance under new, unseen lesions is maximized. Previous analysis has found a strong dependence of the CVs and the prediction error on the specific type of lesioning method used, i.e. on the way in which the activity of lesioned neurons is disrupted. We present a new, informational lesioning method (ILM), which views a lesion as a noisy channel and applies a controlled lesion to the network by varying the lesioning level from large to arbitrarily small magnitudes. Studying the ILM within the FCA framework, our main results are threefold: first, that lower lesioning levels permit more accurate FCA predictions; second, that the usage of minute ILM lesioning levels can uncover the long-term effects of elements on the network's functioning; and third, that as the lesioning level decreases, the CVs tend to approach limit values, reflecting the importance of these elements in the intact, normal-functioning neurocontroller.     

Tell Me Who I Am: An Interactive Recommendation System

We consider a model of recommendation systems, where each member from a given set of players has a binary preference to each element in a given set of objects: intuitively, each player either likes or dislikes each object. However, the players do not know their preferences. To find his preference of an object, a player may probe it, but each probe incurs unit cost. The goal of the players is to learn their complete preference vector (approximately) while incurring minimal cost. This is possible if many players have similar preference vectors: such a set of players with similar “taste” may split the cost of probing all objects among them, and share the results of their probes by posting them on a public billboard. The problem is that players do not know a priori whose taste is close to theirs. In this paper we present a distributed randomized peer-to-peer algorithm in which each player outputs a vector which is close to the best possible approximation of the player’s real preference vector after a polylogarithmic number of rounds. The algorithm works under adversarial preferences. Previous algorithms either made severely limiting assumptions on the structure of the preference vectors, or had polynomial overhead. Research of N. Alon supported in part by the Israel Science Foundation and by the Von Neumann Fund. B. Awerbuch supported by NSF grants ANIR-0240551, CCF-0515080 and CCR-0311795. Research of Y. Azar supported in part by the German-Israeli Foundation and by the Israel Science Foundation. Research of B. Patt-Shamir supported in part by Israel Ministry of Science and Technology and by the Israel Science Foundation (grant 664/05).     

The trithorax group gene moira encodes a brahma-associated putative chromatin-remodeling factor in Drosophila melanogaster

The genes of the trithorax group (trxG) in Drosophila melanogaster are required to maintain the pattern of homeotic gene expression that is established early in embryogenesis by the transient expression of the segmentation genes. The precise role of each of the diverse trxG members and the functional relationships among them are not well understood. Here, we report on the isolation of the trxG gene moira (mor) and its molecular characterization. mor encodes a fruit fly homolog of the human and yeast chromatin-remodeling factors BAF170, BAF155, and SWI3. mor is widely expressed throughout development, and its 170-kDa protein product is present in many embryonic tissues. In vitro, MOR can bind to itself and it interacts with Brahma (BRM), an SWI2-SNF2 homolog, with which it is associated in embryonic nuclear extracts. The leucine zipper motif of MOR is likely to participate in self-oligomerization; the equally conserved SANT domain, for which no function is known, may be required for optimal binding to BRM. MOR thus joins BRM and Snf5-related 1 (SNR1), two known Drosophila SWI-SNF subunits that act as positive regulators of the homeotic genes. These observations provide a molecular explanation for the phenotypic and genetic relationships among several of the trxG genes by suggesting that they encode evolutionarily conserved components of a chromatin-remodeling complex.