Andrea Giovannucci

Bio: Andrea Giovannucci is an academic researcher from University of North Carolina at Chapel Hill. The author has contributed to research in topics: Combinatorial auction & Reverse auction. The author has an hindex of 19, co-authored 66 publications receiving 2253 citations. Previous affiliations of Andrea Giovannucci include Princeton University & Pompeu Fabra University.

CaImAn an open source tool for scalable calcium imaging data analysis

Abstract: The human brain contains billions of cells called neurons that rapidly carry information from one part of the brain to another. Progress in medical research and healthcare is hindered by the difficulty in understanding precisely which neurons are active at any given time. New brain imaging techniques and genetic tools allow researchers to track the activity of thousands of neurons in living animals over many months. However, these experiments produce large volumes of data that researchers currently have to analyze manually, which can take a long time and generate irreproducible results. There is a need to develop new computational tools to analyze such data. The new tools should be able to operate on standard computers rather than just specialist equipment as this would limit the use of the solutions to particularly well-funded research teams. Ideally, the tools should also be able to operate in real-time as several experimental and therapeutic scenarios, like the control of robotic limbs, require this. To address this need, Giovannucci et al. developed a new software package called CaImAn to analyze brain images on a large scale. Firstly, the team developed algorithms that are suitable to analyze large sets of data on laptops and other standard computing equipment. These algorithms were then adapted to operate online in real-time. To test how well the new software performs against manual analysis by human researchers, Giovannucci et al. asked several trained human annotators to identify active neurons that were round or donut-shaped in several sets of imaging data from mouse brains. Each set of data was independently analyzed by three or four researchers who then discussed any neurons they disagreed on to generate a ‘consensus annotation’. Giovannucci et al. then used CaImAn to analyze the same sets of data and compared the results to the consensus annotations. This demonstrated that CaImAn is nearly as good as human researchers at identifying active neurons in brain images. CaImAn provides a quicker method to analyze large sets of brain imaging data and is currently used by over a hundred laboratories across the world. The software is open source, meaning that it is freely-available and that users are encouraged to customize it and collaborate with other users to develop it further.

Efficient and accurate extraction of in vivo calcium signals from microendoscopic video data

Abstract: In vivo calcium imaging through microendoscopic lenses enables imaging of previously inaccessible neuronal populations deep within the brains of freely moving animals. However, it is computationally challenging to extract single-neuronal activity from microendoscopic data, because of the very large background fluctuations and high spatial overlaps intrinsic to this recording modality. Here, we describe a new constrained matrix factorization approach to accurately separate the background and then demix and denoise the neuronal signals of interest. We compared the proposed method against previous independent components analysis and constrained nonnegative matrix factorization approaches. On both simulated and experimental data recorded from mice, our method substantially improved the quality of extracted cellular signals and detected more well-isolated neural signals, especially in noisy data regimes. These advances can in turn significantly enhance the statistical power of downstream analyses, and ultimately improve scientific conclusions derived from microendoscopic data.

An anytime algorithm for optimal coalition structure generation

Abstract: Coalition formation is a fundamental type of interaction that involves the creation of coherent groupings of distinct, autonomous, agents in order to efficiently achieve their individual or collective goals. Forming effective coalitions is a major research challenge in the field of multi-agent systems. Central to this endeavour is the problem of determining which of the many possible coalitions to form in order to achieve some goal. This usually requires calculating a value for every possible coalition, known as the coalition value, which indicates how beneficial that coalition would be if it was formed. Once these values are calculated, the agents usually need to find a combination of coalitions, in which every agent belongs to exactly one coalition, and by which the overall outcome of the system is maximized. However, this coalition structure generation problem is extremely challenging due to the number of possible solutions that need to be examined, which grows exponentially with the number of agents involved. To date, therefore, many algorithms have been proposed to solve this problem using different techniques -- ranging from dynamic programming, to integer programming, to stochastic search -- all of which suffer from major limitations relating to execution time, solution quality, and memory requirements. With this in mind, we develop an anytime algorithm to solve the coalition structure generation problem. Specifically, the algorithm uses a novel representation of the search space, which partitions the space of possible solutions into sub-spaces such that it is possible to compute upper and lower bounds on the values of the best coalition structures in them. These bounds are then used to identify the sub-spaces that have no potential of containing the optimal solution so that they can be pruned. The algorithm, then, searches through the remaining sub-spaces very efficiently using a branch-and-bound technique to avoid examining all the solutions within the searched subspace(s). In this setting, we prove that our algorithm enumerates all coalition structures efficiently by avoiding redundant and invalid solutions automatically. Moreover, in order to effectively test our algorithm we develop a new type of input distribution which allows us to generate more reliable benchmarks compared to the input distributions previously used in the field. Given this new distribution, we show that for 27 agents our algorithm is able to find solutions that are optimal in 0.175% of the time required by the fastest available algorithm in the literature. The algorithm is anytime, and if interrupted before it would have normally terminated, it can still provide a solution that is guaranteed to be within a bound from the optimal one. Moreover, the guarantees we provide on the quality of the solution are significantly better than those provided by the previous state of the art algorithms designed for this purpose. For example, for the worst case distribution given 25 agents, our algorithm is able to find a 90% efficient solution in around 10% of time it takes to find the optimal solution.

NoRMCorre: An online algorithm for piecewise rigid motion correction of calcium imaging data

Abstract: Motion correction is a challenging pre-processing problem that arises early in the analysis pipeline of calcium imaging data sequences. Here we introduce an algorithm for fast Non-Rigid Motion Correction (NoRMCorre) based on template matching. orm operates by splitting the field of view into overlapping spatial patches that are registered for rigid translation against a continuously updated template. The estimated alignments are subsequently up-sampled to create a smooth motion field for each frame that can efficiently approximate non-rigid motion in a piecewise-rigid manner. orm allows for subpixel registration and can be run in an online mode resulting in comparable to or even faster than real time motion registration on streaming data. We evaluate the performance of the proposed method with simple yet intuitive metrics and compare against other non-rigid registration methods on two-photon calcium imaging datasets. Open source Matlab and Python code is also made available.

A sensorimotor account of vision and visual consciousness-Authors' Response-Acting out our sensory experience

Abstract: Many current neurophysiological, psychophysical, and psychological approaches to vision rest on the idea that when we see, the brain produces an internal representation of the world. The activation of this internal representation is assumed to give rise to the experience of seeing. The problem with this kind of approach is that it leaves unexplained how the existence of such a detailed internal representation might produce visual consciousness. An alternative proposal is made here. We propose that seeing is a way of acting. It is a particular way of exploring the environment. Activity in internal representations does not generate the experience of seeing. The outside world serves as its own, external, representation. The experience of seeing occurs when the organism masters what we call the governing laws of sensorimotor contingency. The advantage of this approach is that it provides a natural and principled way of accounting for visual consciousness, and for the differences in the perceived quality of sensory experience in the different sensory modalities. Several lines of empirical evidence are brought forward in support of the theory, in particular: evidence from experiments in sensorimotor adaptation, visual \"filling in,\" visual stability despite eye movements, change blindness, sensory substitution, and color perception.

High-performance calcium sensors for imaging activity in neuronal populations and microcompartments

Abstract: Calcium imaging with genetically encoded calcium indicators (GECIs) is routinely used to measure neural activity in intact nervous systems. GECIs are frequently used in one of two different modes: to track activity in large populations of neuronal cell bodies, or to follow dynamics in subcellular compartments such as axons, dendrites and individual synaptic compartments. Despite major advances, calcium imaging is still limited by the biophysical properties of existing GECIs, including affinity, signal-to-noise ratio, rise and decay kinetics and dynamic range. Using structure-guided mutagenesis and neuron-based screening, we optimized the green fluorescent protein-based GECI GCaMP6 for different modes of in vivo imaging. The resulting jGCaMP7 sensors provide improved detection of individual spikes (jGCaMP7s,f), imaging in neurites and neuropil (jGCaMP7b), and may allow tracking larger populations of neurons using two-photon (jGCaMP7s,f) or wide-field (jGCaMP7c) imaging.

Advancing the understanding of autism disease mechanisms through genetics

Abstract: Progress in understanding the genetic etiology of autism spectrum disorders (ASD) has fueled remarkable advances in our understanding of its potential neurobiological mechanisms. Yet, at the same time, these findings highlight extraordinary causal diversity and complexity at many levels ranging from molecules to circuits and emphasize the gaps in our current knowledge. Here we review current understanding of the genetic architecture of ASD and integrate genetic evidence, neuropathology and studies in model systems with how they inform mechanistic models of ASD pathophysiology. Despite the challenges, these advances provide a solid foundation for the development of rational, targeted molecular therapies.

Suite2p: beyond 10,000 neurons with standard two-photon microscopy

Abstract: Two-photon microscopy of calcium-dependent sensors has enabled unprecedented recordings from vast populations of neurons. While the sensors and microscopes have matured over several generations of development, computational methods to process the resulting movies remain inefficient and can give results that are hard to interpret. Here we introduce Suite2p: a fast, accurate and complete pipeline that registers raw movies, detects active cells, extracts their calcium traces and infers their spike times. Suite2p runs on standard workstations, operates faster than real time, and recovers ~2 times more cells than the previous state-of-the-art method. Its low computational load allows routine detection of ~10,000 cells simultaneously with standard two-photon resonant-scanning microscopes. Recordings at this scale promise to reveal the fine structure of activity in large populations of neurons or large populations of subcellular structures such as synaptic boutons.