Kishore Vasan, Deisy Gysi, Albert-Laszlo Barabasi
The depth of knowledge offered by post-genomic medicine has carried the promise of new drugs, and cures for multiple diseases. To explore the degree to which this capability has materialized, we extract meta-data from 356,403 clinical trials spanning four decades, aiming to offer mechanistic insights into the innovation practices in drug discovery. We find that convention dominates over innovation, as over 96% of the recorded trials focus on previously tested drug targets, and the tested drugs target only 12% of the human interactome. If current patterns persist, it would take 170 years to target all druggable proteins. We uncover two network-based fundamental mechanisms that currently limit target discovery: preferential attachment, leading to the repeated exploration of previously targeted proteins; and local network effects, limiting exploration to proteins interacting with highly explored proteins. We build on these insights to develop a quantitative network-based model of drug discovery. We demonstrate that the model is able to accurately recreate the exploration patterns observed in clinical trials. Most importantly, we show that a network-based search strategy can widen the scope of drug discovery by guiding exploration to novel proteins that are part of under explored regions in the human interactome.

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Alice Patania, Antoine Allard, Jean-Gabriel Young
We study the problem of clustering networks whose nodes have imputed or physical positions in a single dimension, such as prestige hierarchies or the similarity dimension of hyperbolic embeddings. Existing algorithms, such as the critical gap method and other greedy strategies, only offer approximate solutions. Here, we introduce a dynamic programming approach that returns provably optimal solutions in polynomial time — O(n^2) steps — for a broad class of clustering objectives. We demonstrate the algorithm through applications to synthetic and empirical networks, and show that it outperforms existing heuristics by a significant margin, with a similar execution time.

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Chris Kang, Madelynn McElroy, and Nikolaos K. Voulgarakis

Entropy 2023, 25(2), 235

Early embryonic development involves forming all specialized cells from a fluid-like mass of identical stem cells. The differentiation process consists of a series of symmetry-breaking events, starting from a high-symmetry state (stem cells) to a low-symmetry state (specialized cells). This scenario closely resembles phase transitions in statistical mechanics. To theoretically study this hypothesis, we model embryonic stem cell (ESC) populations through a coupled Boolean network (BN) model. The interaction is applied using a multilayer Ising model that considers paracrine and autocrine signaling, along with external interventions. It is demonstrated that cell-to-cell variability can be interpreted as a mixture of steady-state probability distributions. Simulations have revealed that such models can undergo a series of first- and second-order phase transitions as a function of the system parameters that describe gene expression noise and interaction strengths. These phase transitions result in spontaneous symmetry-breaking events that generate new types of cells characterized by various steady-state distributions. Coupled BNs have also been shown to self-organize in states that allow spontaneous cell differentiation.

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Scientists and philosophers have been attempting to define life for ages. In biology class we were taught to define life through the set of features that we, and every other species on the planet share. Things like movement, respiration, growth, and reproduction. Life is made of cells and has DNA. But does biochemistry constitute the whole picture? As far back as 1970, Carl Sagan didn’t think so. Attempts at defining life, he and many others thought, were too constrained by the characteristics of life as we know it. A single example of extraterrestrial life could change everything.

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Theodor Cimpeanu, Francisco C Santos, The Anh Han
Humans have developed considerable machinery used at scale to create policies and to distribute incentives, yet we are forever seeking ways in which to improve upon these, our institutions. Especially when funding is limited, it is imperative to optimise spending without sacrificing positive outcomes, a challenge which has often been approached within several areas of social, life and engineering sciences. These studies often neglect the availability of information, cost restraints, or the underlying complex network structures, which define real-world populations. Here, we have extended these models, including the aforementioned concerns, but also tested the robustness of their findings to stochastic social learning paradigms. Akin to real-world decisions on how best to distribute endowments, we study several incentive schemes, which consider information about the overall population, local neighbourhoods, or the level of influence which a cooperative node has in the network, selectively rewarding cooperative behaviour if certain criteria are met. Following a transition towards a more realistic network setting and stochastic behavioural update rule, we found that carelessly promoting cooperators can often lead to their downfall in socially diverse settings. These emergent cyclic patterns not only damage cooperation, but also decimate the budgets of external investors. Our findings highlight the complexity of designing effective and cogent investment policies in socially diverse populations.

Read the full article at: arxiv.org