Recent studies have shown promising results in the detection of Mild Cognitive Impairment (MCI) using easily accessible Electroencephalogram (EEG) data which would help administer early and effective treatment for dementia patients. However, the reliability and practicality of such systems remains unclear. In this work, we investigate the potential limitations and challenges in developing a robust MCI detection method using two contrasting datasets: 1) CAUEEG, collected and annotated by expert neurologists in controlled settings and 2) GENEEG, a new dataset collected and annotated in general practice clinics, a setting where routine MCI diagnoses are typically made. We find that training on small datasets, as is done by most previous works, tends to produce high variance models that make overconfident predictions, and are unreliable in practice. Additionally, distribution shifts between datasets make cross-domain generalization challenging. Finally, we show that MCI detection using EEG may suffer from fundamental limitations because of the overlapping nature of feature distributions with control groups. We call for more effort in high-quality data collection in actionable settings (like general practice clinics) to make progress towards this salient goal of non-invasive MCI detection.

Leveraging the vast genetic diversity within microbiomes offers unparalleled insights into complex phenotypes, yet the task of accurately predicting and understanding such traits from genomic data remains challenging. We propose a framework taking advantage of existing large models for gene vectorization to predict habitat specificity from entire microbial genome sequences. Based on our model, we develop attribution techniques to elucidate gene interaction effects that drive microbial adaptation to diverse environments. We train and validate our approach on a large dataset of high quality microbiome genomes from different habitats. We not only demonstrate solid predictive performance, but also how sequence-level information of entire genomes allows us to identify gene associations underlying complex phenotypes. Our attribution recovers known important interaction networks and proposes new candidates for experimental follow up.

Prokaryotic viruses, which infect bacteria and archaea, are key players in microbial communities. Predicting the hosts of prokaryotic viruses helps decipher the dynamic relationship between microbes. Experimental methods for host prediction cannot keep pace with the fast accumulation of sequenced phages. Thus, there is a need for computational host prediction. Despite some promising results, computational host prediction remains a challenge because of the limited known interactions and the sheer amount of sequenced phages by high-throughput sequencing technologies. The state-of-the-art methods can only achieve 43\% accuracy at the species level. In this work, we formulate host prediction as link prediction in a knowledge graph that integrates multiple protein and DNA-based sequence features. Our implementation named CHERRY can be applied to predict hosts for newly discovered viruses and to identify viruses infecting targeted bacteria. We demonstrated the utility of CHERRY for both applications and compared its performance with 11 popular host prediction methods. To our best knowledge, CHERRY has the highest accuracy in identifying virus-prokaryote interactions. It outperforms all the existing methods at the species level with an accuracy increase of 37\%. In addition, CHERRY's performance on short contigs is more stable than other tools.

High annotation costs are a substantial bottleneck in applying modern deep learning architectures to clinically relevant medical use cases, substantiating the need for novel algorithms to learn from unlabeled data. In this work, we propose ContIG, a self-supervised method that can learn from large datasets of unlabeled medical images and genetic data. Our approach aligns images and several genetic modalities in the feature space using a contrastive loss. We design our method to integrate multiple modalities of each individual person in the same model end-to-end, even when the available modalities vary across individuals. Our procedure outperforms state-of-the-art self-supervised methods on all evaluated downstream benchmark tasks. We also adapt gradient-based explainability algorithms to better understand the learned cross-modal associations between the images and genetic modalities. Finally, we perform genome-wide association studies on the features learned by our models, uncovering interesting relationships between images and genetic data.

The reconstruction of microbial genomes from large metagenomic datasets is a critical procedure for finding uncultivated microbial populations and defining their microbial functional roles. To achieve that, we need to perform metagenomic binning, clustering the assembled contigs into draft genomes. Despite the existing computational tools, most of them neglect one important property of the metagenomic data, that is, the noise. To further improve the metagenomic binning step and reconstruct better metagenomes, we propose a deep Contrastive Learning framework for Metagenome Binning (CLMB), which can efficiently eliminate the disturbance of noise and produce more stable and robust results. Essentially, instead of denoising the data explicitly, we add simulated noise to the training data and force the deep learning model to produce similar and stable representations for both the noise-free data and the distorted data. Consequently, the trained model will be robust to noise and handle it implicitly during usage. CLMB outperforms the previous state-of-the-art binning methods significantly, recovering the most near-complete genomes on almost all the benchmarking datasets (up to 17\% more reconstructed genomes compared to the second-best method). It also improves the performance of bin refinement, reconstructing 8-22 more high-quality genomes and 15-32 more middle-quality genomes than the second-best result. Impressively, in addition to being compatible with the binning refiner, single CLMB even recovers on average 15 more HQ genomes than the refiner of VAMB and Maxbin on the benchmarking datasets. CLMB is open-source and available at https://github.com/zpf0117b/CLMB/.

Representation learning on temporal interaction graphs (TIG) is to model complex networks with the dynamic evolution of interactions arising in a broad spectrum of problems. Existing dynamic embedding methods on TIG discretely update node embeddings merely when an interaction occurs. They fail to capture the continuous dynamic evolution of embedding trajectories of nodes. In this paper, we propose a two-module framework named ConTIG, a continuous representation method that captures the continuous dynamic evolution of node embedding trajectories. With two essential modules, our model exploit three-fold factors in dynamic networks which include latest interaction, neighbor features and inherent characteristics. In the first update module, we employ a continuous inference block to learn the nodes' state trajectories by learning from time-adjacent interaction patterns between node pairs using ordinary differential equations. In the second transform module, we introduce a self-attention mechanism to predict future node embeddings by aggregating historical temporal interaction information. Experiments results demonstrate the superiority of ConTIG on temporal link prediction, temporal node recommendation and dynamic node classification tasks compared with a range of state-of-the-art baselines, especially for long-interval interactions prediction.

DNA rearrangement processes recombine gene segments that are organized on the chromosome in a variety of ways. The segments can overlap, interleave or one may be a subsegment of another. We use directed graphs to represent segment organizations on a given locus where contigs containing rearranged segments represent vertices and the edges correspond to the segment relationships. Using graph properties we associate a point in a higher dimensional Euclidean space to each graph such that cluster formations and analysis can be performed with methods from topological data analysis. The method is applied to a recently sequenced model organism \textit{Oxytricha trifallax}, a species of ciliate with highly scrambled genome that undergoes massive rearrangement process after conjugation. The analysis shows some emerging star-like graph structures indicating that segments of a single gene can interleave, or even contain all of the segments from fifteen or more other genes in between its segments. We also observe that as many as six genes can have their segments mutually interleaving or overlapping.