Spatial landmark detection and tissue registration with deep learning.

Spatial landmarks are crucial in describing histological features between samples or sites, tracking regions of interest in microscopy, and registering tissue samples within a common coordinate framework. Although other studies have explored unsupervised landmark detection, existing methods are not well-suited for histological image data as they often require a large number of images to converge, are unable to handle nonlinear deformations between tissue sections and are ineffective for z-stack alignment, other modalities beyond image data or multimodal data. We address these challenges by introducing effortless landmark detection, a new unsupervised landmark detection and registration method using neural-network-guided thin-plate splines. Our proposed method is evaluated on a diverse range of datasets including histology and spatially resolved transcriptomics, demonstrating superior performance in both accuracy and stability compared to existing approaches.

Prosit Transformer: A transformer for Prediction of MS2 Spectrum Intensities.

Machine learning has been an integral part of interpreting data from mass spectrometry (MS)-based proteomics for a long time. Relatively recently, a machine-learning structure appeared successful in other areas of bioinformatics, Transformers. Furthermore, the implementation of Transformers within bioinformatics has become relatively convenient due to transfer learning, i.e., adapting a network trained for other tasks to new functionality. Transfer learning makes these relatively large networks more accessible as it generally requires less data, and the training time improves substantially. We implemented a Transformer based on the pretrained model TAPE to predict MS2 intensities. TAPE is a general model trained to predict missing residues from protein sequences. Despite being trained for a different task, we could modify its behavior by adding a prediction head at the end of the TAPE model and fine-tune it using the spectrum intensity from the training set to the well-known predictor Prosit. We demonstrate that the predictor, which we call Prosit Transformer, outperforms the recurrent neural-network-based predictor Prosit, increasing the median angular similarity on its hold-out set from 0.908 to 0.929. We believe that Transformers will significantly increase prediction accuracy for other types of predictions within MS-based proteomics.

Parallelized calculation of permutation tests.

MOTIVATION: Permutation tests offer a straightforward framework to assess the significance of differences in sample statistics. A significant advantage of permutation tests are the relatively few assumptions about the distribution of the test statistic are needed, as they rely on the assumption of exchangeability of the group labels. They have great value, as they allow a sensitivity analysis to determine the extent to which the assumed broad sample distribution of the test statistic applies. However, in this situation, permutation tests are rarely applied because the running time of naïve implementations is too slow and grows exponentially with the sample size. Nevertheless, continued development in the 1980s introduced dynamic programming algorithms that compute exact permutation tests in polynomial time. Albeit this significant running time reduction, the exact test has not yet become one of the predominant statistical tests for medium sample size. Here, we propose a computational parallelization of one such dynamic programming-based permutation test, the Green algorithm, which makes the permutation test more attractive. RESULTS: Parallelization of the Green algorithm was found possible by non-trivial rearrangement of the structure of the algorithm. A speed-up-by orders of magnitude-is achievable by executing the parallelized algorithm on a GPU. We demonstrate that the execution time essentially becomes a non-issue for sample sizes, even as high as hundreds of samples. This improvement makes our method an attractive alternative to, e.g. the widely used asymptotic Mann-Whitney U-test. AVAILABILITYAND IMPLEMENTATION: In Python 3 code from the GitHub repository https://github.com/statisticalbiotechnology/parallelPermutationTest under an Apache 2.0 license. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Spatial multimodal analysis of transcriptomes and metabolomes in tissues.

We present a spatial omics approach that combines histology, mass spectrometry imaging and spatial transcriptomics to facilitate precise measurements of mRNA transcripts and low-molecular-weight metabolites across tissue regions. The workflow is compatible with commercially available Visium glass slides. We demonstrate the potential of our method using mouse and human brain samples in the context of dopamine and Parkinson's disease.