The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens

Background The Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function. Results Here, we report on the results of the third CAFA challenge, CAFA3, that featured an expanded analysis over the previous CAFA rounds, both in terms of volume of data analyzed and the types of analysis performed. In a novel and major new development, computational predictions and assessment goals drove some of the experimental assays, resulting in new functional annotations for more than 1000 genes. Specifically, we performed experimental whole-genome mutation screening in Candida albicans and Pseudomonas aureginosa genomes, which provided us with genome-wide experimental data for genes associated with biofilm formation and motility. We further performed targeted assays on selected genes in Drosophila melanogaster, which we suspected of being involved in long-term memory. Conclusion We conclude that while predictions of the molecular function and biological process annotations have slightly improved over time, those of the cellular component have not. Term-centric prediction of experimental annotations remains equally challenging; although the performance of the top methods is significantly better than the expectations set by baseline methods in C. albicans and D. melanogaster, it leaves considerable room and need for improvement. Finally, we report that the CAFA community now involves a broad range of participants with expertise in bioinformatics, biological experimentation, biocuration, and bio-ontologies, working together to improve functional annotation, computational function prediction, and our ability to manage big data in the era of large experimental screens.Peer reviewe

The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens

BackgroundThe Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function.ResultsHere, we report on the results of the third CAFA challenge, CAFA3, that featured an expanded analysis over the previous CAFA rounds, both in terms of volume of data analyzed and the types of analysis performed. In a novel and major new development, computational predictions and assessment goals drove some of the experimental assays, resulting in new functional annotations for more than 1000 genes. Specifically, we performed experimental whole-genome mutation screening in Candida albicans and Pseudomonas aureginosa genomes, which provided us with genome-wide experimental data for genes associated with biofilm formation and motility. We further performed targeted assays on selected genes in Drosophila melanogaster, which we suspected of being involved in long-term memory.ConclusionWe conclude that while predictions of the molecular function and biological process annotations have slightly improved over time, those of the cellular component have not. Term-centric prediction of experimental annotations remains equally challenging; although the performance of the top methods is significantly better than the expectations set by baseline methods in C. albicans and D. melanogaster, it leaves considerable room and need for improvement. Finally, we report that the CAFA community now involves a broad range of participants with expertise in bioinformatics, biological experimentation, biocuration, and bio-ontologies, working together to improve functional annotation, computational function prediction, and our ability to manage big data in the era of large experimental screens.</p

Multi-Parameter Optimization Design of Axial-Flow Pump Based on Orthogonal Method

The axial-flow pump is a widely used piece of general machinery which consumes large amounts of energy. In this study, an axial-flow pump with the specific speed of 536 is firstly designed and experimentally measured; then, the orthogonal method is employed to conduct the energy performance optimization. Five optimization parameters, including hub control point, hub stagger angle, shroud stagger angle, camber angle and centroid position were set with four levels. Sixteen individual pumps were designed according to the orthogonal method; then, a numerical simulation was implemented to obtain the energy performance and flow pattern. Results showed that the shroud stagger angle has the maximum influence on the pump head and efficiency, and the hub stagger angle and camber angle are also very important. At a design point of flow rate 70 kg/s, the efficiency of the optimal pump is 86.29%, which improved by 2.05% in comparison with the baseline pump. The pressure gradient of the optimal pump from blade inlet to outlet becomes more fluent than that of baseline pump, and the low-velocity region of the optimal pump at the blade head shrinks, compared to that of the baseline pump

Crystallization and Alkaline Degradation Behaviors of Poly(l-Lactide)/4-Armed Poly(ε-Caprolactone)-Block-Poly(d-Lactide) Blends with Different Poly(d-Lactide) Block Lengths

Four-armed poly(&epsilon;-caprolactone)-block-poly(d-lactide) (4-C-D) copolymers with different poly(d-lactide) (PDLA) block lengths (Mn,PDLAs) were synthesized by sequential ring-opening polymerization (ROP). The formation of stereocomplex (SC) crystallites in the 80/20 poly(l-lactide) (PLLA)/4-C-D blends were investigated with the change of Mn,PDLA from 0.5 to 1.5 kg/mol. It was found that the crystallization and alkaline degradation of the blends were profoundly affected by the formed SC crystallites. The PLLA/4-C-D0.5 blend had the lowest crystallization rate of the three blends, and it was difficult to see spherulites in this blend by polarized optical microscopy (POM) observation after isothermal crystallization at 140 &deg;C for 4 h. Meanwhile, when Mn,PDLA was 1 kg/mol or 1.5 kg/mol, SC crystallites could be formed in the PLLA/4-C-D blend and acted as nucleators for the crystallization of PLLA homo-crystals. However, the overall crystallization rates of the two blends were still lower than that of the neat PLLA. In the PLLA/4-C-D1.5 blend, the Raman results showed that small isolated SC spherulites were trapped inside the big PLLA homo-spherulites during isothermal crystallization. The degradation rate of the PLLA/4-C-D blend decreased when Mn,PDLA increased from 0.5 to 1.5 kg/mol, and the degradation morphologies had a close relationship with the crystallization state of the blends. This work revealed the gradual formation of SC crystallites with the increase in Mn,PDLA in the PLLA/4-C-D blends and its significant effect on the crystallization and degradation behaviors of the blend films

Multi-Parameter Optimization Design of Axial-Flow Pump Based on Orthogonal Method

The axial-flow pump is a widely used piece of general machinery which consumes large amounts of energy. In this study, an axial-flow pump with the specific speed of 536 is firstly designed and experimentally measured; then, the orthogonal method is employed to conduct the energy performance optimization. Five optimization parameters, including hub control point, hub stagger angle, shroud stagger angle, camber angle and centroid position were set with four levels. Sixteen individual pumps were designed according to the orthogonal method; then, a numerical simulation was implemented to obtain the energy performance and flow pattern. Results showed that the shroud stagger angle has the maximum influence on the pump head and efficiency, and the hub stagger angle and camber angle are also very important. At a design point of flow rate 70 kg/s, the efficiency of the optimal pump is 86.29%, which improved by 2.05% in comparison with the baseline pump. The pressure gradient of the optimal pump from blade inlet to outlet becomes more fluent than that of baseline pump, and the low-velocity region of the optimal pump at the blade head shrinks, compared to that of the baseline pump

Nanotechnology Lighting the Way for Gene Therapy in Ophthalmopathy: From Opportunities toward Applications

Hereditary ophthalmopathy is a well-described threat to human visual health affecting millions of people. Gene therapy for ophthalmopathy has received widespread attention with the increasing understanding of pathogenic genes. Effective and safe delivery of accurate nucleic acid drugs (NADs) is the core of gene therapy. Efficient nanodelivery and nanomodification technologies, appropriate targeted genes, and the choice of drug injection methods are the guiding lights of gene therapy. Compared with traditional drugs, NADs can specifically change the expression of specific genes or restore the normal function of mutant genes. Nanodelivery carriers can improve targeting and nanomodification can improve the stability of NADs. Therefore, NADs, which can fundamentally solve pathogeny, hold great promise in the treatment of ophthalmopathy. This paper reviews the limitations of ocular disease treatment, discusses the classification of NADs in ophthalmology, reveals the delivery strategies of NADs to improve bioavailability, targeting, and stability, and summarizes the mechanisms of NADs in ophthalmopathy

Table_1_Measuring equality in access to urban parks: A big data analysis from Chengdu.XLSX

Spatial equality of parks is a significant issue in environmental justice studies. In cities with high-density development and limited land resources, this study uses a supply-demand adjusted two-step floating catchment area model (2SFCA), paying attention to residents' subjective preferences and psychological accessibility. It assesses equality of access to urban parks from two dimensions: spatial equality and quantitative equality at a fine scale of 100 × 100 m grid resolution. The spatial equality of urban parks in Chengdu is measured under different transportation modes (walking, cycling, and driving) based on multi-source geospatial big data and machine learning approaches. The results show: (1) There were significant differences in the spatial distribution of park accessibility under different modes of transportation. The spatial distribution under walking was significantly influenced by the park itself, while the distribution of rivers significantly influenced the spatial distribution under cycling and driving; (2) Accessibility to urban parks was almost universally equal in terms of driving, relatively equal in terms of cycling, and seriously unequal in terms of walking; (3) Spatial local autocorrelation analysis shows that park accessibility tended to be significantly clustered, with little spatial variation; and (4) The supply and demand of urban parks were relatively equal. The results can help urban planners to formulate effective strategies to alleviate spatial inequality more reasonably and precisely. The applied research methods can further improve the system of scientific evaluation from a new perspective.</p

Data_Sheet_1_Measuring equality in access to urban parks: A big data analysis from Chengdu.docx

Spatial equality of parks is a significant issue in environmental justice studies. In cities with high-density development and limited land resources, this study uses a supply-demand adjusted two-step floating catchment area model (2SFCA), paying attention to residents' subjective preferences and psychological accessibility. It assesses equality of access to urban parks from two dimensions: spatial equality and quantitative equality at a fine scale of 100 × 100 m grid resolution. The spatial equality of urban parks in Chengdu is measured under different transportation modes (walking, cycling, and driving) based on multi-source geospatial big data and machine learning approaches. The results show: (1) There were significant differences in the spatial distribution of park accessibility under different modes of transportation. The spatial distribution under walking was significantly influenced by the park itself, while the distribution of rivers significantly influenced the spatial distribution under cycling and driving; (2) Accessibility to urban parks was almost universally equal in terms of driving, relatively equal in terms of cycling, and seriously unequal in terms of walking; (3) Spatial local autocorrelation analysis shows that park accessibility tended to be significantly clustered, with little spatial variation; and (4) The supply and demand of urban parks were relatively equal. The results can help urban planners to formulate effective strategies to alleviate spatial inequality more reasonably and precisely. The applied research methods can further improve the system of scientific evaluation from a new perspective.</p