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Lijing Lin

Publications and source records attributed to Lijing Lin.

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CellWorld: From Gene-Level Reconstruction to Latent Cell Prediction in Spatial Transcriptomics Foundation Models

This paper shows that latent-space predictive pretraining can provide a scalable route to foundation models for spatial transcriptomics. Existing spatial transcriptomics foundation models primarily reconstruct masked gene identities or expression values, potentially encouraging the reproduction of assay-specific technical variation and limiting representation transferability. To avoid directly reconstructing such variation, we shift the prediction target from observed gene measurements to latent cell representations and introduce CellWorld, which predicts the latent representations of masked cells from visible spatial context and a limited partial-expression hint. We pretrain four CellWorld variants, spanning 5.74M to 94.56M trainable parameters, on a corpus of 46 million human cells. Our controlled scaling experiments show that performance improves with model capacity, particularly on spatial tasks, while spatial transfer depends more on sufficient optimization and broad biological source diversity than on cell count alone. Across four held-out datasets, even CellWorld-Small, with 5.74M trainable parameters, outperforms every baseline on all 11 linear-probe benchmarks and all seven fine-tuned spatial benchmarks. Most notably, a frozen CellWorld-Large pretrained on only 5\% of the corpus with broad biological source coverage outperforms every fully fine-tuned baseline across all seven spatial benchmarks. Code is available at https://github.com/UoM-HealthAI/CellWorld.

cs.AI

Rethinking RoPE: A Mathematical Blueprint for N-dimensional Positional Embedding

Rotary Position Embedding (RoPE) is widely adopted in large language models (LLMs) due to its efficient encoding of relative positions with strong extrapolation capabilities. However, while its application in higher-dimensional input domains, such as 2D images, have been explored in several attempts, a unified theoretical framework is still lacking. To address this, we propose a systematic mathematical framework for RoPE grounded in Lie group and Lie algebra theory. We derive the necessary and sufficient conditions for any valid $N$-dimensional RoPE based on two core properties of RoPE - relativity and reversibility. We demonstrate that RoPE can be characterized as a basis of a maximal abelian subalgebra (MASA) in the special orthogonal Lie algebra, and that the commonly used axis-aligned block-diagonal RoPE, where each input axis is encoded by an independent 2x2 rotation block, corresponds to the maximal toral subalgebra. Furthermore, we reduce spatial inter-dimensional interactions to a change of basis, resolved by learning an orthogonal transformation. Our experiment results suggest that inter-dimensional interactions should be balanced with local structure preservation. Overall, our framework unifies and explains existing RoPE designs while enabling principled extensions to higher-dimensional modalities and tasks.

cs.LG

A scoping review of causal methods enabling predictions under hypothetical interventions

Background and Aims: The methods with which prediction models are usually developed mean that neither the parameters nor the predictions should be interpreted causally. However, when prediction models are used to support decision making, there is often a need for predicting outcomes under hypothetical interventions. We aimed to identify published methods for developing and validating prediction models that enable risk estimation of outcomes under hypothetical interventions, utilizing causal inference: their main methodological approaches, underlying assumptions, targeted estimands, and potential pitfalls and challenges with using the method, and unresolved methodological challenges. Methods: We systematically reviewed literature published by December 2019, considering papers in the health domain that used causal considerations to enable prediction models to be used for predictions under hypothetical interventions. Results: We identified 4919 papers through database searches and a further 115 papers through manual searches, of which 13 were selected for inclusion, from both the statistical and the machine learning literature. Most of the identified methods for causal inference from observational data were based on marginal structural models and g-estimation. Conclusions: There exist two broad methodological approaches for allowing prediction under hypothetical intervention into clinical prediction models: 1) enriching prediction models derived from observational studies with estimated causal effects from clinical trials and meta-analyses; and 2) estimating prediction models and causal effects directly from observational data. These methods require extending to dynamic treatment regimes, and consideration of multiple interventions to operationalise a clinical decision support system. Techniques for validating 'causal prediction models' are still in their infancy.

stat.ME

Towards a Framework for the Design, Implementation and Reporting of Methodology Scoping Reviews

Background: In view of the growth of published papers, there is an increasing need for studies that summarise scientific research. An increasingly common review is a 'Methodology scoping review', which provides a summary of existing analytical methods, techniques and software, proposed or applied in research articles, which address an analytical problem or further an analytical approach. However, guidelines for their design, implementation and reporting are limited. Methods: Drawing on the experiences of the authors, which were consolidated through a series of face-to-face workshops, we summarise the challenges inherent in conducting a methodology scoping review and offer suggestions of best practice to promote future guideline development. Results: We identified three challenges of conducting a methodology scoping review. First, identification of search terms; one cannot usually define the search terms a priori and the language used for a particular method can vary across the literature. Second, the scope of the review requires careful consideration since new methodology is often not described (in full) within abstracts. Third, many new methods are motivated by a specific clinical question, where the methodology may only be documented in supplementary materials. We formulated several recommendations that build upon existing review guidelines. These recommendations ranged from an iterative approach to defining search terms through to screening and data extraction processes. Conclusion: Although methodology scoping reviews are an important aspect of research, there is currently a lack of guidelines to standardise their design, implementation and reporting. We recommend a wider discussion on this topic.

cs.DL