Novel hypotheses in biomedical research are often developed or validated in model organisms such as mice and zebrafish and thus play a crucial role. However, due to biological differences between species, translating these findings into human applications remains challenging. Moreover, commonly used orthologous gene information is often incomplete and entails a significant information loss during gene-id conversion. To address these issues, we present a novel methodology for species-agnostic transfer learning with heterogeneous domain adaptation. We extended the cross-domain structure-preserving projection toward out-of-sample prediction. Our approach not only allows knowledge integration and translation across various species without relying on gene orthology but also identifies similar GO among the most influential genes composing the latent space for integration. Subsequently, during the alignment of latent spaces, each composed of species-specific genes, it is possible to identify functional annotations of genes missing from public orthology databases. We evaluated our approach with four different single-cell sequencing datasets focusing on cell-type prediction and compared it against related machine-learning approaches. In summary, the developed model outperforms related methods working without prior knowledge when predicting unseen cell types based on other species' data. The results demonstrate that our novel approach allows knowledge transfer beyond species barriers without the dependency on known gene orthology but utilizing the entire gene sets.

The multi-omics molecular characterization of cancer opened a new horizon for our understanding of cancer biology and therapeutic strategies. However, a tumor biopsy comprises diverse types of cells limited not only to cancerous cells but also to tumor microenvironmental cells and adjacent normal cells. This heterogeneity is a major confounding factor that hampers a robust and reproducible bioinformatic analysis for biomarker identification using multi-omics profiles. Besides, the heterogeneity itself has been recognized over the years for its significant prognostic values in some cancer types, thus offering another promising avenue for therapeutic intervention. A number of computational approaches to unravel such heterogeneity from high-throughput molecular profiles of a tumor sample have been proposed, but most of them rely on the data from an individual omics layer. Since the heterogeneity of cells is widely distributed across multi-omics layers, methods based on an individual layer can only partially characterize the heterogeneous admixture of cells. To help facilitate further development of the methodologies that synchronously account for several multi-omics profiles, we wrote a comprehensive review of diverse approaches to characterize tumor heterogeneity based on three different omics layers: genome, epigenome and transcriptome. As a result, this review can be useful for the analysis of multi-omics profiles produced by many large-scale consortia. Contact:[email protected].

Motivation: A large number of newly sequenced proteins are generated by the next-generation sequencing technologies and the biochemical function assignment of the proteins is an important task. However, biological experiments are too expensive to characterize such a large number of protein sequences, thus protein function prediction is primarily done by computational modeling methods, such as profile Hidden Markov Model (pHMM) and k-mer based methods. Nevertheless, existing methods have some limitations; k-mer based methods are not accurate enough to assign protein functions and pHMM is not fast enough to handle large number of protein sequences from numerous genome projects. Therefore, a more accurate and faster protein function prediction method is needed. Results: In this paper, we introduce DeepFam, an alignment-free method that can extract functional information directly from sequences without the need of multiple sequence alignments. In extensive experiments using the Clusters of Orthologous Groups (COGs) and G protein-coupled receptor (GPCR) dataset, DeepFam achieved better performance in terms of accuracy and runtime for predicting functions of proteins compared to the state-of-the-art methods, both alignment-free and alignment-based methods. Additionally, we showed that DeepFam has a power of capturing conserved regions to model protein families. In fact, DeepFam was able to detect conserved regions documented in the Prosite database while predicting functions of proteins. Our deep learning method will be useful in characterizing functions of the ever increasing protein sequences. Availability and implementation: Codes are available at https://bhi-kimlab.github.io/DeepFam.