Ju, K. | bioRxiv Science

bioRxiv2024

De novo multi-mechanism antimicrobial peptide design via multimodal deep learning

Artificial intelligence (AI)-driven discovery of antimicrobial peptides (AMPs) is yet to fully utilise their three-dimensional (3D) structural characteristics, microbial specie-specific antimicrobial activities and mechanisms. Here, we constructed a QLAPD database comprising the sequence, structures and antimicrobial properties of 12,914 AMPs. QLAPD underlies a multimodal, multitask, multilabel, and conditionally controlled AMP discovery (M3-CAD) pipeline, which is proposed for the de novo design of multi-mechanism AMPs to combat multidrug-resistant organisms (MDROs). This pipeline integrates the generation, regression, and classification modules, using a innovative 3D voxel coloring method to capture the nuanced physicochemical context of amino acids, significantly enhancing structural characterizations. QL-AMP-1, discovered by M3-CAD, which possesses four antimicrobial mechanisms, exhibited low toxicity and significant activity against MDROs. The skin wound infection model demonstrates its considerable antimicrobial effects and negligible toxicity. Altogether, integrating 3D features, specie-specific antimicrobial activities and mechanisms enhanced AI-driven AMP discovery, making the M3-CAD pipeline a viable tool for de novo AMP design.

bioengineering↗

bioRxiv2019

The socioeconomic burden of severe mental disorder in China, 2014-2017: a prevalence study

Mental illness is a chronic disease with high morbidity and mortality rate, resulting in heavy economic burden for family and society, especially the severe ones. Chinese government has taken a series of action on the treatment and management of severe mental disorder (SMD), but the scale of economic burden caused by SMD was still unclear. In this paper, we applied prevalence-based bottom-up approach to estimate the direct and indirect economic burden of SMD in Southwest China from 2014 to 2017. We used the sampled inpatient medical record data of patient with SMD to calculate the total direct cost and estimated the indirect economic burden using human capital approach.The total ecomonic burden of SMD was USD9,733 million and direct burden was contiributed for 7.5% as USD734.5 million in four years total. The growth rate of direct medical cost was declined due to the health policy reform and total cost control policy. The indirect cost was rapidly increased in four years when estimated with DALYs reported in GBD2010 and resulting USD8,998.6 million. We next estimated the indirect burden using sample DALYs and occupation wage cost approach as sensitive analysis. We found that the indirect burden was sensitive to the key variable and the estimation approach, but the estimates share same increasing trend but with different velocity. Our study suggests that SMD in China have posed substantial economic burden at individual and social levels, with the appropriate estimation of total economic burden, our reaserch would attract more attention and be helpful for health resources distribution.

scientific communication and education↗