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Computational models are invaluable in capturing the complexities of real-world biological processes. Yet, the selection of appropriate algorithms for inference tasks, especially when dealing with real-world observational data, remains a challenging and underexplored area. This gap has spurred the development of various parameter estimation algorithms, particularly within the realm of Simulation-Based Inference (SBI), such as neural and statistical SBI methods. Limited research exists on how to make informed choices on SBI methods when faced with real-world data, which often results in some form of model misspecification. In this paper, we provide comprehensive guidelines for deciding between SBI approaches for complex biological models. We apply the guidelines to two agent-based models that describe cellular dynamics using real-world data. Our study unveils a critical insight: while neural SBI methods demand significantly fewer simulations for inference results, they tend to yield biased estimations, a trend persistent even with robust variants of these algorithms. On the other hand, the accuracy of statistical SBI methods enhances substantially as the number of simulations increases. This finding suggests that, given a sufficient computational budget, statistical SBI can surpass neural SBI in performance. Our results not only shed light on the efficacy of different SBI methodologies in real-world scenarios but also suggest potential avenues for enhancing neural SBI approaches. This study is poised to be a useful resource for computational biologists navigating the intricate landscape of SBI in biological modeling.

Social technology research today largely focuses on mitigating the negative impacts of technology and, therefore, often misses the potential of technology to enhance human connections and well-being. However, we see a potential to shift towards a holistic view of social technology's impact on human flourishing. We introduce Positive Social Technology (Positech), a framework that shifts emphasis toward leveraging social technologies to support and augment human flourishing. This workshop is organized around three themes relevant to Positech: 1) "Exploring Relevant and Adjacent Research" to define and widen the Positech scope with insights from related fields, 2) "Projecting the Landscape of Positech" for participants to outline the domain's key aspects and 3) "Envisioning the Future of Positech," anchored around strategic planning towards a sustainable research community. Ultimately, this workshop will serve as a platform to shift the narrative of social technology research towards a more positive, human-centric approach. It will foster research that goes beyond fixing technologies to protect humans from harm, to also pursue enriching human experiences and connections through technology.

Simulation based inference (SBI) methods enable the estimation of posterior distributions when the likelihood function is intractable, but where model simulation is feasible. Popular neural approaches to SBI are the neural posterior estimator (NPE) and its sequential version (SNPE). These methods can outperform statistical SBI approaches such as approximate Bayesian computation (ABC), particularly for relatively small numbers of model simulations. However, we show in this paper that the NPE methods are not guaranteed to be highly accurate, even on problems with low dimension. In such settings the posterior cannot be accurately trained over the prior predictive space, and even the sequential extension remains sub-optimal. To overcome this, we propose preconditioned NPE (PNPE) and its sequential version (PSNPE), which uses a short run of ABC to effectively eliminate regions of parameter space that produce large discrepancy between simulations and data and allow the posterior emulator to be more accurately trained. We present comprehensive empirical evidence that this melding of neural and statistical SBI methods improves performance over a range of examples, including a motivating example involving a complex agent-based model applied to real tumour growth data., Comment: 31 pages, 11 figures

Generative AI systems have been heralded as tools for augmenting human creativity and inspiring divergent thinking, though with little empirical evidence for these claims. This paper explores the effects of exposure to AI-generated images on measures of design fixation and divergent thinking in a visual ideation task. Through a between-participants experiment (N=60), we found that support from an AI image generator during ideation leads to higher fixation on an initial example. Participants who used AI produced fewer ideas, with less variety and lower originality compared to a baseline. Our qualitative analysis suggests that the effectiveness of co-ideation with AI rests on participants' chosen approach to prompt creation and on the strategies used by participants to generate ideas in response to the AI's suggestions. We discuss opportunities for designing generative AI systems for ideation support and incorporating these AI tools into ideation workflows., Comment: Accepted at the CHI Conference on Human Factors in Computing Systems (CHI 24),18 pages, 15 figures

Music is a valuable non-pharmacological tool that provides benefits for people with dementia, and there is interest in designing technologies to support music use in dementia care. To ensure music technologies are appropriately designed for supporting caregivers and people living with dementia, there remains a need to better understand how music is currently used in everyday care at home. We aimed to understand how people with dementia and their caregivers use music technologies in everyday caring, as well as challenges they experience using music and technology. This study used a mixed methods design. A survey was completed by 77 caregivers and people with dementia to understand their use of music and technology. Of these, 18 survey respondents (12 family caregivers, 6 people living with dementia) participated in focus groups about their experiences of using music and technology in care. Transcripts were analysed with reflexive thematic analysis. Most survey respondents used music often in their daily lives, reporting a range of music technologies such as CDs, radio, and streaming. Focus groups highlighted benefits and challenges of music technologies in everyday care. Participants used music and music technologies to regulate mood, provide joy, facilitate social connection, encourage reminiscence, provide continuity before and after diagnosis, and to make caregiving easier. Challenges of using music technology in care included difficulties staying up to date with evolving technology, and low self-efficacy for technology use expressed by people living with dementia. Evidently, people living with dementia and their caregivers use music technologies to support their everyday care needs. Results suggest opportunities to design technologies enabling easier access to music and supporting people living with dementia with recreational and therapeutic music listening and music-based activities.

Recent innovations in digital technology offer significant opportunities for older adults to engage in meaningful activities. To investigate older adults' perceptions of using existing and emerging technologies for meaningful activities, we conducted three participatory design workshops and follow-up interviews with adults aged over 65. The workshops encompassed discussions on existing technologies for meaningful activities, demonstrations of emerging technologies such as VR, AR, and AI, and design activities including prototyping and storyboarding. Our findings show that while participants had diverse interpretations of meaningful activities, they sought to use technologies to support continuity in the pursuit of these activities. Specifically, participants highlighted the importance of safe aging at home, which provides a pathway for meaningful activities in later life. We further discuss participants' discerning attitudes when assessing the use of different technologies for meaningful activities and several values and attributes they desire when envisioning future technologies, including simplicity, positivity, proactivity, and integration.

Biological sequence analysis relies on the ability to denoise the imprecise output of sequencing platforms. We consider a common setting where a short sequence is read out repeatedly using a high-throughput long-read platform to generate multiple subreads, or noisy observations of the same sequence. Denoising these subreads with alignment-based approaches often fails when too few subreads are available or error rates are too high. In this paper, we propose a novel method for blindly denoising sets of sequences without directly observing clean source sequence labels. Our method, Self-Supervised Set Learning (SSSL), gathers subreads together in an embedding space and estimates a single set embedding as the midpoint of the subreads in both the latent and sequence spaces. This set embedding represents the "average" of the subreads and can be decoded into a prediction of the clean sequence. In experiments on simulated long-read DNA data, SSSL methods denoise small reads of $\leq 6$ subreads with 17% fewer errors and large reads of $>6$ subreads with 8% fewer errors compared to the best baseline. On a real dataset of antibody sequences, SSSL improves over baselines on two self-supervised metrics, with a significant improvement on difficult small reads that comprise over 60% of the test set. By accurately denoising these reads, SSSL promises to better realize the potential of high-throughput DNA sequencing data for downstream scientific applications.

It is shown that laminar vortex rings can be generated by impulsive body forces having particular spatial and temporal characteristics. The method produces vortex rings in a fluid initially at rest, and once generated, the flow field automatically satisfies the boundary conditions and is divergence-free. Numerical simulations and analytical models show that the strength of these rings can be accurately predicted by considering diffusion alone, despite the nonlinear nature of the generation process. A particularly simple model, which approximates the source of vorticity within vertical slabs, is proposed. This model predicts the ring circulation almost as accurately as a model which uses the exact geometry of the source of vorticity. It is found that when the duration of the force is less than a time scale based on the force radius and fluid viscosity, the ring circulation can be predicted accurately using an inviscid model., Comment: 37 pages, 11 figures

Simulation-based inference techniques are indispensable for parameter estimation of mechanistic and simulable models with intractable likelihoods. While traditional statistical approaches like approximate Bayesian computation and Bayesian synthetic likelihood have been studied under well-specified and misspecified settings, they often suffer from inefficiencies due to wasted model simulations. Neural approaches, such as sequential neural likelihood (SNL) avoid this wastage by utilising all model simulations to train a neural surrogate for the likelihood function. However, the performance of SNL under model misspecification is unreliable and can result in overconfident posteriors centred around an inaccurate parameter estimate. In this paper, we propose a novel SNL method, which through the incorporation of additional adjustment parameters, is robust to model misspecification and capable of identifying features of the data that the model is not able to recover. We demonstrate the efficacy of our approach through several illustrative examples, where our method gives more accurate point estimates and uncertainty quantification than SNL.

Deep generative models have emerged as a popular machine learning-based approach for inverse design problems in the life sciences. However, these problems often require sampling new designs that satisfy multiple properties of interest in addition to learning the data distribution. This multi-objective optimization becomes more challenging when properties are independent or orthogonal to each other. In this work, we propose a Pareto-compositional energy-based model (pcEBM), a framework that uses multiple gradient descent for sampling new designs that adhere to various constraints in optimizing distinct properties. We demonstrate its ability to learn non-convex Pareto fronts and generate sequences that simultaneously satisfy multiple desired properties across a series of real-world antibody design tasks.

Analyzing proteins from single cells by tandem mass spectrometry (MS) has become technically feasible. While such analysis has the potential to accurately quantify thousands of proteins across thousands of single cells, the accuracy and reproducibility of the results may be undermined by numerous factors affecting experimental design, sample preparation, data acquisition, and data analysis. Broadly accepted community guidelines and standardized metrics will enhance rigor, data quality, and alignment between laboratories. Here we propose best practices, quality controls, and data reporting recommendations to assist in the broad adoption of reliable quantitative workflows for single-cell proteomics., Comment: Supporting website: https://single-cell.net/guidelines

All human diseases involve proteins, yet our current tools to characterize and quantify them are limited. To better elucidate proteins across space, time, and molecular composition, we provide provocative projections for technologies to meet the challenges that protein biology presents. With a broad perspective, we discuss grand opportunities to transition the science of proteomics into a more propulsive enterprise. Extrapolating recent trends, we offer potential futures for a next generation of disruptive approaches to define, quantify and visualize the multiple dimensions of the proteome, thereby transforming our understanding and interactions with human disease in the coming decade., Comment: Submitted to Nature. 22 Pages. 6 Figures. Corresponding author Neil L. Kelleher