Showing papers by "Albert-László Barabási published in 2008"

Understanding individual human mobility patterns

Abstract: The mapping of large-scale human movements is important for urban planning, traffic forecasting and epidemic prevention. Work in animals had suggested that their foraging might be explained in terms of a random walk, a mathematical rendition of a series of random steps, or a Levy flight, a random walk punctuated by occasional larger steps. The role of Levy statistics in animal behaviour is much debated — as explained in an accompanying News Feature — but the idea of extending it to human behaviour was boosted by a report in 2006 of Levy flight-like patterns in human movement tracked via dollar bills. A new human study, based on tracking the trajectory of 100,000 cell-phone users for six months, reveals behaviour close to a Levy pattern, but deviating from it as individual trajectories show a high degree of temporal and spatial regularity: work and other commitments mean we are not as free to roam as a foraging animal. But by correcting the data to accommodate individual variation, simple and predictable patterns in human travel begin to emerge. The cover photo (by Cesar Hidalgo) captures human mobility in New York's Grand Central Station. This study used a sample of 100,000 mobile phone users whose trajectory was tracked for six months to study human mobility patterns. Displacements across all users suggest behaviour close to the Levy-flight-like pattern observed previously based on the motion of marked dollar bills, but with a cutoff in the distribution. The origin of the Levy patterns observed in the aggregate data appears to be population heterogeneity and not Levy patterns at the level of the individual. Despite their importance for urban planning1, traffic forecasting2 and the spread of biological3,4,5 and mobile viruses6, our understanding of the basic laws governing human motion remains limited owing to the lack of tools to monitor the time-resolved location of individuals. Here we study the trajectory of 100,000 anonymized mobile phone users whose position is tracked for a six-month period. We find that, in contrast with the random trajectories predicted by the prevailing Levy flight and random walk models7, human trajectories show a high degree of temporal and spatial regularity, each individual being characterized by a time-independent characteristic travel distance and a significant probability to return to a few highly frequented locations. After correcting for differences in travel distances and the inherent anisotropy of each trajectory, the individual travel patterns collapse into a single spatial probability distribution, indicating that, despite the diversity of their travel history, humans follow simple reproducible patterns. This inherent similarity in travel patterns could impact all phenomena driven by human mobility, from epidemic prevention to emergency response, urban planning and agent-based modelling.

High-Quality Binary Protein Interaction Map of the Yeast Interactome Network

Abstract: Current yeast interactome network maps contain several hundred molecular complexes with limited and somewhat controversial representation of direct binary interactions. We carried out a comparative quality assessment of current yeast interactome data sets, demonstrating that high-throughput yeast two-hybrid (Y2H) screening provides high-quality binary interaction information. Because a large fraction of the yeast binary interactome remains to be mapped, we developed an empirically controlled mapping framework to produce a "second-generation" high-quality, high-throughput Y2H data set covering approximately 20% of all yeast binary interactions. Both Y2H and affinity purification followed by mass spectrometry (AP/MS) data are of equally high quality but of a fundamentally different and complementary nature, resulting in networks with different topological and biological properties. Compared to co-complex interactome models, this binary map is enriched for transient signaling interactions and intercomplex connections with a highly significant clustering between essential proteins. Rather than correlating with essentiality, protein connectivity correlates with genetic pleiotropy.

Uncovering individual and collective human dynamics from mobile phone records

Abstract: Novel aspects of human dynamics and social interactions are investigated by means of mobile phone data. Using extensive phone records resolved in both time and space, we study the mean collective behavior at large scales and focus on the occurrence of anomalous events. We discuss how these spatiotemporal anomalies can be described using standard percolation theory tools. We also investigate patterns of calling activity at the individual level and show that the interevent time of consecutive calls is heavy-tailed. This finding, which has implications for dynamics of spreading phenomena in social networks, agrees with results previously reported on other human activities.

Burstiness and memory in complex systems

Abstract: The dynamics of a wide range of real systems, from email patterns to earthquakes, display a bursty, intermittent nature, characterized by short timeframes of intense activity followed by long times of no or reduced activity. The understanding of the origin of such bursty patterns is hindered by the lack of tools to compare different systems using a common framework. Here we propose to characterize the bursty nature of real signals using orthogonal measures quantifying two distinct mechanisms leading to burstiness: the interevent time distribution and the memory. We find that while the burstiness of natural phenomena is rooted in both the interevent time distribution and memory, for human dynamics memory is weak, and the bursty character is due to the changes in the interevent time distribution. Finally, we show that current models lack in their ability to reproduce the activity pattern observed in real systems, opening up avenues for future work. Copyright c �EPLA, 2008

The implications of human metabolic network topology for disease comorbidity

Abstract: Most diseases are the consequence of the breakdown of cellular processes, but the relationships among genetic/epigenetic defects, the molecular interaction networks underlying them, and the disease phenotypes remain poorly understood. To gain insights into such relationships, here we constructed a bipartite human disease association network in which nodes are diseases and two diseases are linked if mutated enzymes associated with them catalyze adjacent metabolic reactions. We find that connected disease pairs display higher correlated reaction flux rate, corresponding enzyme-encoding gene coexpression, and higher comorbidity than those that have no metabolic link between them. Furthermore, the more connected a disease is to other diseases, the higher is its prevalence and associated mortality rate. The network topology-based approach also helps to uncover potential mechanisms that contribute to their shared pathophysiology. Thus, the structure and modeled function of the human metabolic network can provide insights into disease comorbidity, with potentially important consequences for disease diagnosis and prevention.

Predicting synthetic rescues in metabolic networks.

Abstract: An important goal of medical research is to develop methods to recover the loss of cellular function due to mutations and other defects. Many approaches based on gene therapy aim to repair the defective gene or to insert genes with compensatory function. Here, we propose an alternative, network-based strategy that aims to restore biological function by forcing the cell to either bypass the functions affected by the defective gene, or to compensate for the lost function. Focusing on the metabolism of single-cell organisms, we computationally study mutants that lack an essential enzyme, and thus are unable to grow or have a significantly reduced growth rate. We show that several of these mutants can be turned into viable organisms through additional gene deletions that restore their growth rate. In a rather counterintuitive fashion, this is achieved via additional damage to the metabolic network. Using flux balance-based approaches, we identify a number of synthetically viable gene pairs, in which the removal of one enzyme-encoding gene results in a non-viable phenotype, while the deletion of a second enzyme-encoding gene rescues the organism. The systematic network-based identification of compensatory rescue effects may open new avenues for genetic interventions.

Impact of the solvent capacity constraint on E. coli metabolism.

Abstract: Obtaining quantitative predictions for cellular metabolic activities requires the identification and modeling of the physicochemical constraints that are relevant at physiological growth conditions Molecular crowding in a cell's cytoplasm is one such potential constraint, as it limits the solvent capacity available to metabolic enzymes Using a recently introduced flux balance modeling framework (FBAwMC) here we demonstrate that this constraint determines a metabolic switch in E coli cells when they are shifted from low to high growth rates The switch is characterized by a change in effective optimization strategy, the excretion of acetate at high growth rates, and a global reorganization of E coli metabolic fluxes, the latter being partially confirmed by flux measurements of central metabolic reactions These results implicate the solvent capacity as an important physiological constraint acting on E coli cells operating at high metabolic rates and for the activation of a metabolic switch when they are shifted from low to high growth rates The relevance of this constraint in the context of both the aerobic ethanol excretion seen in fast growing yeast cells (Crabtree effect) and the aerobic glycolysis observed in rapidly dividing cancer cells (Warburg effect) should be addressed in the future

Predicting individual disease risk based on medical history

Abstract: The monumental cost of health care, especially for chronic disease treatment, is quickly becoming unmanageable. This crisis has motivated the drive towards preventative medicine, where the primary concern is recognizing disease risk and taking action at the earliest signs. However, universal testing is neither time nor cost efficient. We propose CARE, a Collaborative Assessment and Recommendation Engine, which relies only on a patient's medical history using ICD-9-CM codes in order to predict future diseases risks. CARE uses collaborative filtering to predict each patient's greatest disease risks based on their own medical history and that of similar patients. We also describe an Iterative version, ICARE, which incorporates ensemble concepts for improved performance. These novel systems require no specialized information and provide predictions for medical conditions of all kinds in a single run. We present experimental results on a Medicare dataset, demonstrating that CARE and ICARE perform well at capturing future disease risks.

Distribution of Node Characteristics in Complex Networks

Abstract: Our enhanced ability to map the structure of various complex networks is increasingly accompanied by the possibility of independently identifying the functional characteristics of each node. Although this led to the observation that nodes with similar characteristics have a tendency to link to each other, in general we lack the tools to quantify the interplay between node properties and the structure of the underlying network. Here we show that when nodes in a network belong to two distinct classes, two independent parameters are needed to capture the detailed interplay between the network structure and node properties. We find that the network structure significantly limits the values of these parameters, requiring a phase diagram to uniquely characterize the configurations available to the system. The phase diagram shows a remarkable independence from the network size, a finding that, together with a proposed heuristic algorithm, allows us to determine its shape even for large networks. To test the usefulness of the developed methods, we apply them to biological and socioeconomic systems, finding that protein functions and mobile phone usage occupy distinct regions of the phase diagram, indicating that the proposed parameters have a strong discriminating power.

Disease diagnoses-bases disease prediction

Abstract: A system for predicting future disease for a subject comprising: a population information set comprising population disease diagnoses for members of a population; a subject-specific information set comprising at least one subject-specific disease diagnosis; and a diagnoses-based prediction module configured to predict one or more future diseases for the subject based on said subject-specific disease diagnosis and said population disease diagnoses for population members having at least one disease in common with the subject.

Impact of Limited Solvent Capacity on Metabolic Rate, Enzyme Activities, and Metabolite Concentrations of S. cerevisiae Glycolysis

Abstract: The cell’s cytoplasm is crowded by its various molecular components, resulting in a limited solvent capacity for the allocation of new proteins, thus constraining various cellular processes such as metabolism. Here we study the impact of the limited solvent capacity constraint on the metabolic rate, enzyme activities, and metabolite concentrations using a computational model of Saccharomyces cerevisiae glycolysis as a case study. We show that given the limited solvent capacity constraint, the optimal enzyme activities and the metabolite concentrations necessary to achieve a maximum rate of glycolysis are in agreement with their experimentally measured values. Furthermore, the predicted maximum glycolytic rate determined by the solvent capacity constraint is close to that measured in vivo. These results indicate that the limited solvent capacity is a relevant constraint acting on S. cerevisiae at physiological growth conditions, and that a full kinetic model together with the limited solvent capacity constraint can be used to predict both metabolite concentrations and enzyme activities in vivo.

Predicting synthetic rescues in metabolic networks

Abstract: An important goal of medical research is to develop methods to recover the loss of cellular function due to mutations and other defects. Many approaches based on gene therapy aim to repair the defective gene or to insert genes with compensatory function. Here, we propose an alternative, network-based strategy that aims to restore biological function by forcing the cell to either bypass the functions affected by the defective gene, or to compensate for the lost function. Focusing on the metabolism of single-cell organisms, we computationally study mutants that lack an essential enzyme, and thus are unable to grow or have a significantly reduced growth rate. We show that several of these mutants can be turned into viable organisms through additional gene deletions that restore their growth rate. In a rather counterintuitive fashion, this is achieved via additional damage to the metabolic network. Using flux balance-based approaches, we identify a number of synthetically viable gene pairs, in which the removal of one enzyme-encoding gene results in a nonviable phenotype, while the deletion of a second enzyme-encoding gene rescues the organism. The systematic network-based identification of compensatory rescue effects may open new avenues for genetic interventions.

Two-dimensional particle motion in a random potential under ac bias

Abstract: Driven diffusion in random media is a much studied problem impacting on a number of various fields. By now, it is well established that the interplay between the annealed randomness of the diffusion process and the quenched randomness of the media gives raise to unexpected scaling phenomena that have been extensively studied in recent decades [1, 2, 3]. The range of applicability of the problem of driven diffusive motion in random media covers various fields, with relaxation phenomena in spin glasses [4], dislocation motion in disordered crystals [5], transport in porous media [6], and turbu lent diffusion [7] being but a few typical examples. In the presence of an external ac field, the motion of a particle is the result of the combined effect of thermally activated diffusivity and periodic motion, induced by the coupling to the applied field. A t time scales much larger than the period of the driving force, one would expect that the influence of the field is negligible and the dynamics of the system can be described by the classical Brownian motion. Indeed, while the particle moves back and forth along the direction of the ac field, a stroboscopic view of the system, obtained by taking pictures only at times that are integer multiples of the external field period, woul d still show a randomly diffusing particle, almost as if the ex ternal field was absent in the system. In contrast to this intuiti ve picture, we demonstrate that the presence of an external ac field can fundamentally change the nature of the dynamics, when quenched randomness is present in the system.