Species-agnostic transfer learning for cross-species transcriptomics data integration without gene orthology.

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.

Gene-gene interaction of AhRwith and within the Wntcascade affects susceptibility to lung cancer.

BACKGROUND: Aberrant Wnt signalling, regulating cell development and stemness, influences the development of many cancer types. The Aryl hydrocarbon receptor (AhR) mediates tumorigenesis of environmental pollutants. Complex interaction patterns of genes assigned to AhR/Wnt-signalling were recently associated with lung cancer susceptibility. AIM: To assess the association and predictive ability of AhR/Wnt-genes with lung cancer in cases and controls of European descent. METHODS: Odds ratios (OR) were estimated for genomic variants assigned to the Wnt agonist and the antagonistic genes DKK2, DKK3, DKK4, FRZB, SFRP4 and Axin2. Logistic regression models with variable selection were trained, validated and tested to predict lung cancer, at which other previously identified SNPs that have been robustly associated with lung cancer risk could also enter the model. Furthermore, decision trees were created to investigate variant × variant interaction. All analyses were performed for overall lung cancer and for subgroups. RESULTS: No genome-wide significant association of AhR/Wnt-genes with overall lung cancer was observed, but within the subgroups of ever smokers (e.g., maker rs2722278 SFRP4; OR = 1.20; 95% CI 1.13-1.27; p = 5.6 × 10-10) and never smokers (e.g., maker rs1133683 Axin2; OR = 1.27; 95% CI 1.19-1.35; p = 1.0 × 10-12). Although predictability is poor, AhR/Wnt-variants are unexpectedly overrepresented in optimized prediction scores for overall lung cancer and for small cell lung cancer. Remarkably, the score for never-smokers contained solely two AhR/Wnt-variants. The optimal decision tree for never smokers consists of 7 AhR/Wnt-variants and only two lung cancer variants. CONCLUSIONS: The role of variants belonging to Wnt/AhR-pathways in lung cancer susceptibility may be underrated in main-effects association analysis. Complex interaction patterns in individuals of European descent have moderate predictive capacity for lung cancer or subgroups thereof, especially in never smokers.