Conceptual design method driven by product genes

Genetics-based design is an effective approach to develop novel products for conceptual design. It could reduce innovation blindness by providing logically structured procedure. However, the major challenge of genetics-based engineering method is that how to identify what information is genetic information and how to use it in a conceptual design process. To solve this problem, this article proposes a conceptual design method driven by product genes. First, a functional expansion model is established based on analyzing the conceptual design process. Second, to respectively compare the functions and structure schemes in the model to biological traits and proteins, a product gene definition composed of behaviors and attributes is put forward. Then, a modeling and coding method of product genes is given analogous to that of biological genes. Third, operation technologies of product genes are analyzed, including breakdown, crossover, recombination, transcription, and translation. Based on this, a conceptual design method driven by product genes is advanced. Finally, an example shows that this method is able to extract key information of products and gives a method of how to use the information in a conceptual design process. Moreover, structure schemes obtained through this method are of high feasibility and have more possibilities of innovation.

Distinct genomic hallmarks exist between metastatic upper and lower tract urothelial carcinoma.

371 Background: Although the genomic landscape of LTUC is well studied, less is known about UTUC, including in the metastatic sites. We compared genomic features of metastatic UTUC and LTUC. Methods: We performed whole exome sequencing on 7 rapid autopsy patients with metastatic UC, with matched primary and metastatic tumor samples (N = 37). Single nucleotide variants (SNV) were identified using Mutect and Strelka. Focused analyses were performed on mutations with known significance in UC as well as mutations predicted to have functional impact using 11 mutation assessors. Genome scale copy number aberrations (CNA) were estimated using Sequenza (normalized for ploidy) to derive gene definition restricted copy number estimation outcomes. Multi-dimensional scaling (MDS) was used to visualize how copy number and mutation-derived genomic distances differed between LTUC and UTUC. Results: Three pts with UTUC (3 primary samples, 13 metastases) and four pts with LTUC (4 primary samples, 17 metastases) were examined. The majority of patients were male (5) and received cisplatin-based therapy (5). We found that SNV burden (mean mutation per megabase) was significantly higher in LTUC vs. UTUC overall (6.6 vs. 3.8, p = 0.001) and when stratified by primaries (6.1 vs. 2.9, p = 0.047); or metastases (6.7 vs. 4.1, p = 0.001). Mutational signature analysis revealed higher proportion of APOBEC signature in all LTUC vs. UTUC tumors. Both inter- and intra-individual genomic distances between primary and metastatic tissues were substantially larger in UTUC than LTUC, suggesting a wider spectrum of mutations at the level of individual nucleotides and chromosomal structure. Interestingly, Gene definition-restricted CNA analysis revealed MDM2 amplification exclusively in UTUC tumors which was associated with shallow p53 deletion. Conclusions: Metastatic UTUC appears to have a lower overall mutational burden but greater genomic variability compared to LTUC. Our relatively small dataset suggests that metastatic UTUC displays a greater spectrum of mutational divergence from LTUC which may partially explain differences in clinical behavior.