Bioinformatics has undergone a paradigm shift in artificial intelligence (AI), particularly through foundation models (FMs), which address longstanding challenges in bioinformatics such as limited annotated data and data noise. These AI techniques have demonstrated remarkable efficacy across various downstream validation tasks, effectively representing diverse biological entities and heralding a new era in computational biology. The primary goal of this survey is to conduct a general investigation and summary of FMs in bioinformatics, tracing their evolutionary trajectory, current research landscape, and methodological frameworks. Our primary focus is on elucidating the application of FMs to specific biological problems, offering insights to guide the research community in choosing appropriate FMs for tasks like sequence analysis, structure prediction, and function annotation. Each section delves into the intricacies of the targeted challenges, contrasting the architectures and advancements of FMs with conventional methods and showcasing their utility across different biological domains. Further, this review scrutinizes the hurdles and constraints encountered by FMs in biology, including issues of data noise, model interpretability, and potential biases. This analysis provides a theoretical groundwork for understanding the circumstances under which certain FMs may exhibit suboptimal performance. Lastly, we outline prospective pathways and methodologies for the future development of FMs in biological research, facilitating ongoing innovation in the field. This comprehensive examination not only serves as an academic reference but also as a roadmap for forthcoming explorations and applications of FMs in biology.

Dynamical control of cellular microenvironments is highly desirable to study complex processes such as stem cell differentiation and immune signaling. We present an ultra-multiplexed microfluidic system for high-throughput single-cell analysis in precisely defined dynamic signaling environments. Our system delivers combinatorial and time-varying signals to 1500 independently programmable culture chambers in week-long live-cell experiments by performing nearly 10⁶ pipetting steps, where single cells, two-dimensional (2D) populations, or 3D neurospheres are chemically stimulated and tracked. Using our system and statistical analysis, we investigated the signaling landscape of neural stem cell differentiation and discovered “cellular logic rules” that revealed the critical role of signal timing and sequence in cell fate decisions. We find synergistic and antagonistic signal interactions and show that differentiation pathways are highly redundant. Our system allows dissection of hidden aspects of cellular dynamics and enables accelerated biological discovery.

Typically, estimating genetic parameters, such as disease heritability and between-disease genetic correlations, demands large datasets containing all relevant phenotypic measures and detailed knowledge of family relationships or, alternatively, genotypic and phenotypic data for numerous unrelated individuals. Here, we suggest an alternative, efficient estimation approach through the construction of two disease metrics from large health datasets: temporal disease prevalence curves and low-dimensional disease embeddings. We present eleven thousand heritability estimates corresponding to five study types: twins, traditional family studies, health records-based family studies, single nucleotide polymorphisms, and polygenic risk scores. We also compute over six hundred thousand estimates of genetic, environmental and phenotypic correlations. Furthermore, we find that: (1) disease curve shapes cluster into five general patterns; (2) early-onset diseases tend to have lower prevalence than late-onset diseases (Spearman’s ρ = 0.32, p < 10^–16); and (3) the disease onset age and heritability are negatively correlated (ρ = −0.46, p < 10^–16).

Zoonotic infections, characterized with huge pathogen diversity, wide affecting area and great society harm, have become a major global public health problem. Early and accurate prediction of their outbreaks is crucial for disease control. The aim of this study was to develop zoonotic diseases risk predictive models based on time-series incidence data and three zoonotic diseases in mainland China were employed as cases. The incidence data for schistosomiasis, echinococcosis, and leptospirosis were downloaded from the Scientific Data Centre of the National Ministry of Health of China, and were processed by interpolation, dynamic curve reconstruction and time series decomposition. Data were decomposed into three distinct components: the trend component, the seasonal component, and the residual component. The trend component was used as input to construct the Long Short-Term Memory (LSTM) prediction model, while the seasonal component was used in the comparison of the periods and amplitudes. Finaly, the accuracy of the hybrid LSTM prediction model was comprehensive evaluated. This study employed trend series of incidence numbers and incidence rates of three zoonotic diseases for modeling. The prediction results of the model showed that the predicted incidence number and incidence rate were very close to the real incidence data. Model evaluation revealed that the prediction error of the hybrid LSTM model was smaller than that of the single LSTM. Thus, these results demonstrate that using trending sequences as input sequences for the model leads to better-fitting predictive models. Our study successfully developed LSTM hybrid models for disease outbreak risk prediction using three zoonotic diseases as case studies. We demonstrate that the LSTM, when combined with time series decomposition, delivers more accurate results compared to conventional LSTM models using the raw data series. Disease outbreak trends can be predicted more accurately using hybrid models.