COllective INtelligence with task assignment

In this paper we study the COllective INtelligence (COIN) framework of Wolpert et al. for dispersion games (Grenager, Powers and Shoham, 2002) and variants of the EL Farol Bar problem. These settings constitute difficult MAS problems where fine-grained coordination between the agents is required. We enhance the COIN framework to dramatically improve convergence results for MAS with a large number of agents. The increased convergence properties for the dispersion games are competitive with especially tailored strategies for solving dispersion games. The enhancements to the COIN framework proved to be essential to solve the more complex variants of the El Farol Bar-like problem

COllective INtelligence with sequences of actions

The design of a Multi-Agent System (MAS) to perform well on a collective task is non-trivial. Straightforward application of learning in a MAS can lead to sub optimal solutions as agents compete or interfere. The COllective INtelligence (COIN) framework of Wolpert et al. proposes an engineering solution for MASs where agents learn to focus on actions which support a common task. As a case study, we investigate the performance of COIN for representative token retrieval problems found to be difficult for agents using classic Reinforcement Learning (RL). We further investigate several techniques from RL (model-based learning, $Q(lambda))$ to scale application of the COIN framework. Lastly, the COIN framework is extended to improve performance for sequences of actions

Foresighted policy gradient reinforcement learning: solving large-scale social dilemmas with rational altruistic punishment

Many important and difficult problems can be modeled as “social dilemmas”, like Hardin's Tragedy of the Commons or the classic iterated Prisoner's Dilemma. It is well known that in these problems, it can be rational for self-interested agents to promote and sustain cooperation by altruistically dispensing costly punishment to other agents, thus maximizing their own long-term reward. However, self-interested agents using most current multi-agent reinforcement learning algorithms will not sustain cooperation in social dilemmas: the algorithms do not sufficiently capture the consequences on the agent's reward of the interactions that it has with other agents. Recent more foresighted algorithms specifically account for such expected consequences, and have been shown to work well for the small-scale Prisoner's Dilemma. However, this approach quickly becomes intractable for larger social dilemmas. Here, we advance on this work and develop a “teach/learn” stateless foresighted policy gradient reinforcement learning algorithm that applies to Social Dilemma's with negative, unilateral side-payments, in the from of costly punishment. In this setting, the algorithm allows agents to learn the most rewarding actions to take with respect to both the dilemma (Cooperate/Defect) and the “teaching” of other agent's behavior through the dispensing of punishment. Unlike other algorithms, we show that this approach scales well to large settings like the Tragedy of the Commons. We show for a variety of settings that large groups of self-interested agents using this algorithm will robustly find and sustain cooperation in social dilemmas where adaptive agents can punish the behavior of other similarly adaptive agents

Learning from induced changes in opponent (re)actions in multi-agent games

Multi-agent learning is a growing area of research. An important topic is to formulate how an agent can learn a good policy in the face of adaptive, competitive opponents. Most research has focused on extensions of single agent learning techniques originally designed for agents in more static environments. These techniques however fail to incorporate a notion of the effect of own previous actions on the development of the policy of the other agents in the system. We argue that incorporation of this property is beneficial in competitive settings. In this paper, we present a novel algorithm to capture this notion, and present experimental results to validate our claim

A decommitment strategy in a competitive multi-agent transportation setting

Decommitment is the action of foregoing of a contract for another (superior) offer. It has been shown that, using decommitment, agents can reach higher utility levels in case of negotiations with uncertainty about future prospects. In this paper, we study the decommitment concept for the novel setting of a large-scale logistics setting with multiple, competing companies. Orders for transportation of loads are acquired by agents of the (competing) companies by bidding in online auctions. We find significant increases in profit when the agents can decommit and postpone the transportation of a load to a more suitable time. Furthermore, we analyze the circumstances for which decommitment has a positive impact if agents are capable of handling multiple contracts simultaneously

Personalized Proteome: Comparing Proteogenomics and Open Variant Search Approaches for Single Amino Acid Variant Detection

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Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Skewed X-inactivation is common in the general female population

X-inactivation is a well-established dosage compensation mechanism ensuring that X-chromosomal genes are expressed at comparable levels in males and females. Skewed X-inactivation is often explained by negative selection of one of the alleles. We demonstrate that imbalanced expression of the paternal and maternal X-chromosomes is common in the general population and that the random nature of the X-inactivation mechanism can be sufficient to explain the imbalance. To this end, we analyzed blood-derived RNA and whole-genome sequencing data from 79 female children and their parents from the Genome of the Netherlands project. We calculated the median ratio of the paternal over total counts at all X-chromosomal heterozygous single-nucleotide variants with coverage ≥10. We identified two individuals where the same X-chromosome was inactivated in all cells. Imbalanced expression of the two X-chromosomes (ratios ≤0.35 or ≥0.65) was observed in nearly 50% of the population. The empirically observed skewing is explained by a theoretical model where X-inactivation takes place in an embryonic stage in which eight cells give rise to the hematopoietic compartment. Genes escaping X-inactivation are expressed from both alleles and therefore demonstrate less skewing than inactivated genes. Using this characteristic, we identified three novel escapee genes (SSR4, REPS2, and SEPT6), but did not find support for many previously reported escapee genes in blood. Our collective data suggest that skewed X-inactivation is common in the general population. This may contribute to manifestation of symptoms in carriers of recessive X-linked disorders. We recommend that X-inactivation results should not be used lightly in the interpretation of X-linked variants

Solve-RD: systematic pan-European data sharing and collaborative analysis to solve rare diseases.

For the first time in Europe hundreds of rare disease (RD) experts team up to actively share and jointly analyse existing patient's data. Solve-RD is a Horizon 2020-supported EU flagship project bringing together >300 clinicians, scientists, and patient representatives of 51 sites from 15 countries. Solve-RD is built upon a core group of four European Reference Networks (ERNs; ERN-ITHACA, ERN-RND, ERN-Euro NMD, ERN-GENTURIS) which annually see more than 270,000 RD patients with respective pathologies. The main ambition is to solve unsolved rare diseases for which a molecular cause is not yet known. This is achieved through an innovative clinical research environment that introduces novel ways to organise expertise and data. Two major approaches are being pursued (i) massive data re-analysis of >19,000 unsolved rare disease patients and (ii) novel combined -omics approaches. The minimum requirement to be eligible for the analysis activities is an inconclusive exome that can be shared with controlled access. The first preliminary data re-analysis has already diagnosed 255 cases form 8393 exomes/genome datasets. This unprecedented degree of collaboration focused on sharing of data and expertise shall identify many new disease genes and enable diagnosis of many so far undiagnosed patients from all over Europe