A generative model for constructing nucleic acid sequences binding to a protein.

BACKGROUND: Interactions between protein and nucleic acid molecules are essential to a variety of cellular processes. A large amount of interaction data generated by high-throughput technologies have triggered the development of several computational methods either to predict binding sites in a sequence or to determine whether a pair of sequences interacts or not. Most of these methods treat the problem of the interaction of nucleic acids with proteins as a classification problem rather than a generation problem. RESULTS: We developed a generative model for constructing single-stranded nucleic acids binding to a target protein using a long short-term memory (LSTM) neural network. Experimental results of the generative model are promising in the sense that DNA and RNA sequences generated by the model for several target proteins show high specificity and that motifs present in the generated sequences are similar to known protein-binding motifs. CONCLUSIONS: Although these are preliminary results of our ongoing research, our approach can be used to generate nucleic acid sequences binding to a target protein. In particular, it will help design efficient in vitro experiments by constructing an initial pool of potential aptamers that bind to a target protein with high affinity and specificity.

Comparative Analysis of Gene Correlation Networks of Breast Cancer Patients Based on Mutations in TP53.

Breast cancer is one of the most prevalent cancers in females, with more than 450,000 deaths each year worldwide. Among the subtypes of breast cancer, basal-like breast cancer, also known as triple-negative breast cancer, shows the lowest survival rate and does not have effective treatments yet. Somatic mutations in the TP53 gene frequently occur across all breast cancer subtypes, but comparative analysis of gene correlations with respect to mutations in TP53 has not been done so far. The primary goal of this study is to identify gene correlations in two groups of breast cancer patients and to derive potential prognostic gene pairs for breast cancer. We partitioned breast cancer patients into two groups: one group with a mutated TP53 gene (mTP53) and the other with a wild-type TP53 gene (wtTP53). For every gene pair, we computed the hazard ratio using the Cox proportional hazard model and constructed gene correlation networks (GCNs) enriched with prognostic information. Our GCN is more informative than typical GCNs in the sense that it indicates the type of correlation between genes, the concordance index, and the prognostic type of a gene. Comparative analysis of correlation patterns and survival time of the two groups revealed several interesting findings. First, we found several new gene pairs with opposite correlations in the two GCNs and the difference in their correlation patterns was the most prominent in the basal-like subtype of breast cancer. Second, we obtained potential prognostic genes for breast cancer patients with a wild-type TP53 gene. From a comparative analysis of GCNs of mTP53 and wtTP53, we found several gene pairs that show significantly different correlation patterns in the basal-like breast cancer subtype and obtained prognostic genes for patients with a wild-type TP53 gene. The GCNs and prognostic genes identified in this study will be informative for the prognosis of survival and for selecting a drug target for breast cancer, in particular for basal-like breast cancer. To the best of our knowledge, this is the first attempt to construct GCNs for breast cancer patients with or without mutations in the TP53 gene and to find prognostic genes accordingly.