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Climate change is a health emergency, impacting multiple facets of human well-being via direct and indirect pathways. Nature Climate Change asked experts from different health fields to share their thoughts on the urgent issues and possible paths forward.

Zhao et al. used single-cell and spatial multiomics data analysis of human and mouse lung adenocarcinoma tumors and cell lines to reveal TP53 mutation-associated changes in cancer cells and their microenvironment.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

We will probably overshoot our current climate targets, so policies of adaptation and recovery need much more attention, say Martin Parry, Jason Lowe and Clair Hanson.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Circulating tumour DNA profiling in early-stage non-small-cell lung cancer can be used to track single-nucleotide variants in plasma to predict lung cancer relapse and identify tumour subclones involved in the metastatic process.

Inventory data from more than 1 million trees across African, Amazonian and Southeast Asian tropical forests suggests that, despite their high diversity, just 1,053 species, representing a consistent ~2.2% of tropical tree species in each region, constitute half of Earth’s 800 billion tropical trees.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS) infers B cell and T cell fractions from whole-genome sequencing data. Applied to the 100,000 Genomes Project datasets, circulating T cell fraction provides sex-dependent and prognostic insights in patients.

Basolateral recycling and transcytotic pathways in epithelial cells are defined by specific markers, however the apical recycling pathway is poorly understood. Perez Bay et al. show that Megalin is a marker for this pathway, which intersects with the other routes in shared perinuclear recycling endosomes.

The authors define molecular mechanisms by which distinct domains of the ubiquitin editing enzyme A20 contribute to the regulation of inflammation and cell death.

Mutations that dysregulate Notch1 and Ras/PI3K signalling are common in T-cell acute lymphoblastic leukaemia; here, treatment with a PI3K inhibitor is shown to induce drug resistance that is associated with downregulation of activated Notch1 signalling, suggesting that inhibition of both Notch1 and PI3K could promote drug resistance.

How well can we predict future sea level rise?

Knowledge of how climate change will affect temperatures on a regional scale is needed for effective planning and preparedness. This study uses five climate models to investigate regional warming. It shows that warming is nonlinear for doublings of atmospheric CO₂ and that nonlinearity increases with higher CO₂ concentrations.

Swanton and colleagues present a clonal expression signature, ORACLE, which, in combination with clinicopathological and molecular risk factors, can predict survival of patients with lung adenocarcinoma, and they prospectively validate its prognostic value.

Bacterial divisome protein FtsA, which is an actin homologue, forms double filaments following binding to FtsN, and like MreB, an actin homologue in the elongasome, the curvature-sensing double filaments guide peptidoglycan insertion for cell division.

Engineering biosynthetic assembly lines is a powerful path to new natural products but is challenging with current methods. Here the authors use CRISPR-Cas9 to exchange subdomains within NRPS to alter substrate selectivity.

The ‘pathway’ the world needs to follow to limit global temperature rise to 2 °C remains uncertain. Analysis that takes technical and economic constraints on reducing emissions into account indicates that emissions need to peak in the next decade and then fall rapidly to have a good chance of achieving this goal.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

Some aspects of the Earth system—such as global mean temperatures, and sea-level rise due to thermal expansion or melting of large ice sheets—continue to respond to climate change long after the stabilization of radiative forcing. Simulations with a coupled climate–vegetation model show that similarly ecosystems may be committed to significant change after climate stabilization.

A study using a newly developed framework shows how future peak temperature is related to cumulative emissions of long-lived greenhouse gases such as carbon dioxide and sustained emissions of shorter-lived species such as methane, and suggests an approach for limiting future warming to 2 °C above pre-industrial levels.

High-throughput sequencing of RNA fragments generated from a single-strand RNA-specific nuclease followed by novel computational analysis yields structural insights into noncoding RNA at the transcriptome level.

The effect of a cumulative emission of carbon on peak global mean surface temperature is better constrained than the effect of stabilizing the atmospheric composition. The approach is also insensitive to the timing or peak rate of emissions. Using carbon cycle models, it is shown that a trillion tonnes of carbon emissions (about half of which has already been emitted since industrialization began) will produce a most likely peak warming of 2 degrees Celsius.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Emerging limitations on climate and low-carbon technology would require adjusting our 15.C climate change mitigation pathways. However, this could increase average annual emissions reductions to around 3GtCO₂/year using a broad portfolio of mitigation measures.

Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

It is often assumed that each additional degree of global warming impacts regional climate equally. Here, Goodet al. use the CMIP5 archive to show different precipitation changes arise from 0–2 K versus 2–4 K of warming above pre-industrial levels, partly from nonlinearity in underlying physical mechanisms.

A number of natural occurring small-molecule splicing modulators are known. Here, the authors combine chemogenomic, structural and biochemical methods and show that these compounds also target the spliceosome-associated protein PHF5A and propose a potential modulator binding site in the PHF5A–SF3B1 complex.

In the TRACERx cohort of 171 patients with lung cancer, the ultrasensitive detection of ctDNA improves preoperative patient stratification, also in early-stage disease.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

The response of tropical precipitation to variation in sea surface temperature is stronger than in most climate models, with cool and warm ocean regions linked by strong shallow atmospheric circulations.

Assessing global mean temperature rise using the average warming over the previous one or two decades will delay formal recognition of when Earth breaches the Paris agreement’s 1.5 °C guard rail. Here is what’s needed to avoid the wait.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

Multi-ancestry genome-wide analyses identify variants near UGT2A1 and UGT2A2 associated with COVID-19-related loss of smell or taste. Both genes are expressed in the olfactory epithelium and play a role in metabolizing odorants.

The next step after sequencing a genome is to figure out how the cell actually uses it as an instruction manual. A large international consortium has examined 1% of the genome for what part is transcribed, where proteins are bound, what the chromatin structure looks like, and how the sequence compares to that of other organisms.

Anaerobic gut fungi are a functionally important component of mammalian herbivores’ microbiomes. Here, the authors surveys anaerobic gut fungi in 34 species of ruminants and hindgut fermenters, assessing their patterns and identifying 56 novel genera.

Both emissions reduction and adaptation will need to be much stronger than currently planned if dangerous global impacts of climate change are to be avoided. June's UN talks in Bonn and July's G8 summit present opportunities for world leaders to face this challenge.