First passage time analysis of spatial mutation patterns reveals sub-clonal evolutionary dynamics in colorectal cancer.

The signature of early cancer dynamics on the spatial arrangement of tumour cells is poorly understood, and yet could encode information about how sub-clones grew within the expanding tumour. Novel methods of quantifying spatial tumour data at the cellular scale are required to link evolutionary dynamics to the resulting spatial architecture of the tumour. Here, we propose a framework using first passage times of random walks to quantify the complex spatial patterns of tumour cell population mixing. First, using a simple model of cell mixing we demonstrate how first passage time statistics can distinguish between different pattern structures. We then apply our method to simulated patterns of mutated and non-mutated tumour cell population mixing, generated using an agent-based model of expanding tumours, to explore how first passage times reflect mutant cell replicative advantage, time of emergence and strength of cell pushing. Finally, we explore applications to experimentally measured human colorectal cancer, and estimate parameters of early sub-clonal dynamics using our spatial computational model. We infer a wide range of sub-clonal dynamics, with mutant cell division rates varying between 1 and 4 times the rate of non-mutated cells across our sample set. Some mutated sub-clones emerged after as few as 100 non-mutant cell divisions, and others only after 50,000 divisions. The majority were consistent with boundary driven growth or short-range cell pushing. By analysing multiple sub-sampled regions in a small number of samples, we explore how the distribution of inferred dynamics could inform about the initial mutational event. Our results demonstrate the efficacy of first passage time analysis as a new methodology in spatial analysis of solid tumour tissue, and suggest that patterns of sub-clonal mixing can provide insights into early cancer dynamics.

A link model approach to identify congestion hotspots.

Congestion emerges when high demand peaks put transportation systems under stress. Understanding the interplay between the spatial organization of demand, the route choices of citizens and the underlying infrastructures is thus crucial to locate congestion hotspots and mitigate the delay. Here we develop a model where links are responsible for the processing of vehicles, which can be solved analytically before and after the onset of congestion, and provide insights into the global and local congestion. We apply our method to synthetic and real transportation networks, observing a strong agreement between the analytical solutions and the Monte Carlo simulations, and a reasonable agreement with the travel times observed in 12 cities under congested phase. Our framework can incorporate any type of routing extracted from real trajectory data to provide a more detailed description of congestion phenomena, and could be used to dynamically adapt the capacity of road segments according to the flow of vehicles, or reduce congestion through hotspot pricing.

Mapping nonlocal relationships between metadata and network structure with metadata-dependent encoding of random walks.

Integrating structural information and metadata, such as gender, social status, or interests, enriches networks and enables a better understanding of the large-scale structure of complex systems. However, existing approaches to augment networks with metadata for community detection only consider immediately adjacent nodes and cannot exploit the nonlocal relationships between metadata and large-scale network structure present in many spatial and social systems. Here, we develop a flow-based community detection framework based on the map equation that integrates network information and metadata of distant nodes and reveals more complex relationships. We analyze social and spatial networks and find that our methodology can detect functional metadata-informed communities distinct from those derived solely from network information or metadata. For example, in a mobility network of London, we identify communities that reflect the heterogeneity of income distribution, and in a European power grid network, we identify communities that capture relationships between geography and energy prices beyond country borders.

Impact of urban structure on infectious disease spreading.

The ongoing SARS-CoV-2 pandemic has been holding the world hostage for several years now. Mobility is key to viral spreading and its restriction is the main non-pharmaceutical interventions to fight the virus expansion. Previous works have shown a connection between the structural organization of cities and the movement patterns of their residents. This puts urban centers in the focus of epidemic surveillance and interventions. Here we show that the organization of urban flows has a tremendous impact on disease spreading and on the amenability of different mitigation strategies. By studying anonymous and aggregated intra-urban flows in a variety of cities in the United States and other countries, and a combination of empirical analysis and analytical methods, we demonstrate that the response of cities to epidemic spreading can be roughly classified in two major types according to the overall organization of those flows. Hierarchical cities, where flows are concentrated primarily between mobility hotspots, are particularly vulnerable to the rapid spread of epidemics. Nevertheless, mobility restrictions in such types of cities are very effective in mitigating the spread of a virus. Conversely, in sprawled cities which present many centers of activity, the spread of an epidemic is much slower, but the response to mobility restrictions is much weaker and less effective. Investing resources on early monitoring and prompt ad-hoc interventions in more vulnerable cities may prove helpful in containing and reducing the impact of future pandemics.

Uncovering the socioeconomic facets of human mobility.

Given the rapid recent trend of urbanization, a better understanding of how urban infrastructure mediates socioeconomic interactions and economic systems is of vital importance. While the accessibility of location-enabled devices as well as large-scale datasets of human activities, has fueled significant advances in our understanding, there is little agreement on the linkage between socioeconomic status and its influence on movement patterns, in particular, the role of inequality. Here, we analyze a heavily aggregated and anonymized summary of global mobility and investigate the relationships between socioeconomic status and mobility across a hundred cities in the US and Brazil. We uncover two types of relationships, finding either a clear connection or little-to-no interdependencies. The former tend to be characterized by low levels of public transportation usage, inequitable access to basic amenities and services, and segregated clusters of communities in terms of income, with the latter class showing the opposite trends. Our findings provide useful lessons in designing urban habitats that serve the larger interests of all inhabitants irrespective of their economic status.

Diffusion segregation and the disproportionate incidence of COVID-19 in African American communities.

One of the most concerning aspects of the ongoing COVID-19 pandemic is that it disproportionately affects people from some specific ethnic and socio-economic minorities. In particular, since from the beginning of the pandemic it has been clear that people from Black and African American backgrounds seem to be hit especially hard by the virus, creating a substantial infection gap. The observed abnormal impact on these ethnic groups could probably be due to the co-occurrence of other known risk factors, including co-morbidity, poverty, level of education, access to healthcare, residential segregation and response to cures, although those factors do not seem able to explain fully and in depth the excess incidence of infections and deaths among African Americans. Here, we introduce the concept of diffusion segregation, that is the extent to which a given group of people is internally clustered or exposed to other groups, as a result of mobility and commuting habits. By analysing census and mobility data on major US cities, we found that the weekly excess COVID-19 incidence and mortality in African American communities at the beginning of the COVID-19 pandemic is significantly associated with their level of diffusion segregation. The results confirm that knowing where people commute to, rather than where they live, is potentially much more important to contain and curb the spreading of infectious diseases.

Scaling in the recovery of urban transportation systems from massive events.

Public transportation is a fundamental infrastructure for life in cities. Although its capacity is prepared for daily demand, congestion may rise when huge crowds gather in demonstrations, concerts or sport events. In this work, we study the robustness of public transportation networks by means of a stylized model mimicking individual mobility through the system. We find scaling relations in the delay suffered by both event participants and other citizens doing their usual traveling in the background. The delay is a function of the number of participants and the event location. The model is solved analytically in lattices proving the existence of scaling relations and the connection of their exponents to the local dimension. Thereafter, extensive and systematic simulations in eight worldwide cities reveal that a newly proposed measure of local dimension explains the exponents found in the network recovery. Our methodology allows to dynamically probe the local dimensionality of a transportation network and identify the most vulnerable spots in cities for the celebration of massive events.

Hierarchical organization of urban mobility and its connection with city livability.

The recent trend of rapid urbanization makes it imperative to understand urban characteristics such as infrastructure, population distribution, jobs, and services that play a key role in urban livability and sustainability. A healthy debate exists on what constitutes optimal structure regarding livability in cities, interpolating, for instance, between mono- and poly-centric organization. Here anonymous and aggregated flows generated from three hundred million users, opted-in to Location History, are used to extract global Intra-urban trips. We develop a metric that allows us to classify cities and to establish a connection between mobility organization and key urban indicators. We demonstrate that cities with strong hierarchical mobility structure display an extensive use of public transport, higher levels of walkability, lower pollutant emissions per capita and better health indicators. Our framework outperforms previous metrics, is highly scalable and can be deployed with little cost, even in areas without resources for traditional data collection.

Field theory for recurrent mobility.

Understanding human mobility is crucial for applications such as forecasting epidemic spreading, planning transport infrastructure and urbanism in general. While, traditionally, mobility information has been collected via surveys, the pervasive adoption of mobile technologies has brought a wealth of (real time) data. The easy access to this information opens the door to study theoretical questions so far unexplored. In this work, we show for a series of worldwide cities that commuting daily flows can be mapped into a well behaved vector field, fulfilling the divergence theorem and which is, besides, irrotational. This property allows us to define a potential for the field that can become a major instrument to determine separate mobility basins and discern contiguous urban areas. We also show that empirical fluxes and potentials can be well reproduced and analytically characterized using the so-called gravity model, while other models based on intervening opportunities have serious difficulties.