Comprehensive assessment of mRNA isoform detection methods for long-read sequencing data.

The advancement of Long-Read Sequencing (LRS) techniques has significantly increased the length of sequencing to several kilobases, thereby facilitating the identification of alternative splicing events and isoform expressions. Recently, numerous computational tools for isoform detection using long-read sequencing data have been developed. Nevertheless, there remains a deficiency in comparative studies that systemically evaluate the performance of these tools, which are implemented with different algorithms, under various simulations that encompass potential influencing factors. In this study, we conducted a benchmark analysis of thirteen methods implemented in nine tools capable of identifying isoform structures from long-read RNA-seq data. We evaluated their performances using simulated data, which represented diverse sequencing platforms generated by an in-house simulator, RNA sequins (sequencing spike-ins) data, as well as experimental data. Our findings demonstrate IsoQuant as a highly effective tool for isoform detection with LRS, with Bambu and StringTie2 also exhibiting strong performance. These results offer valuable guidance for future research on alternative splicing analysis and the ongoing improvement of tools for isoform detection using LRS data.

Optimal reactive nitrogen control pathways identified for cost-effective PM2.5 mitigation in Europe.

Excess reactive nitrogen (Nr), including nitrogen oxides (NOx) and ammonia (NH3), contributes strongly to fine particulate matter (PM2.5) air pollution in Europe, posing challenges to public health. Designing cost-effective Nr control roadmaps for PM2.5 mitigation requires considering both mitigation efficiencies and implementation costs. Here we identify optimal Nr control pathways for Europe by integrating emission estimations, air quality modeling, exposure-mortality modeling, Nr control experiments and cost data. We find that phasing out Nr emissions would reduce PM2.5 by 2.3 ± 1.2 µg·m-3 in Europe, helping many locations achieve the World Health Organization (WHO) guidelines and reducing PM2.5-related premature deaths by almost 100 thousand in 2015. Low-ambition NH3 controls have similar PM2.5 mitigation efficiencies as NOx in Eastern Europe, but are less effective in Western Europe until reductions exceed 40%. The efficiency for NH3 controls increases at high-ambition reductions while NOx slightly decreases. When costs are considered, strategies for both regions uniformly shift in favor of NH3 controls, as NH3 controls up to 50% remain 5-11 times more cost-effective than NOx per unit PM2.5 reduction, emphasizing the priority of NH3 control policies for Europe.

Air quality, nitrogen use efficiency and food security in China are improved by cost-effective agricultural nitrogen management.

China's gains in food production over the past four decades have been associated with substantial agricultural nitrogen losses, which contribute to air and water pollution, greenhouse gas emissions and damage to human health. Here, we explore the potential to improve agricultural production practices that simultaneously increase yields while addressing these environmental challenges. We link agronomic research with air quality modelling for an integrated assessment of four improved nitrogen management strategies: improved farm management practices with nitrogen use reductions; machine deep placement of fertilizer; enhanced-efficiency fertilizer use; and improved manure management. We find that simultaneous implementation of the four strategies provides the largest benefits, which include: reductions in PM2.5 concentrations and associated premature deaths; increases in grain yields and grain nitrogen use efficiency; reductions in NO3- leaching and runoff and greenhouse gas emissions. Total benefits of US$30 billion per year exceed the US$18 billion per year in costs. Our findings indicate that policies that improve farmers' agricultural nitrogen management in China will improve both food security and public health while addressing multiple environmental challenges. Similar increases in attention on agricultural policy around the world are likely to provide large benefits in food security, environmental integrity and public health.