A Correction to this paper has been published: https://doi.org/10.1038/s41587-021-00831-9.

Coexisting microbial cells of the same species often exhibit genetic variation that can affect phenotypes ranging from nutrient preference to pathogenicity. Here we present inStrain, a program that uses metagenomic paired reads to profile intra-population genetic diversity (microdiversity) across whole genomes and compares microbial populations in a microdiversity-aware manner, greatly increasing the

Nonlinear data visualization methods, such as t-distributed stochastic neighbor embedding (t-SNE) and uniform manifold approximation and projection (UMAP), summarize the complex transcriptomic landscape of single cells in two dimensions or three dimensions, but they neglect the local density of data points in the original space, often resulting in misleading visualizations where densely populated subsets

Single-cell transcriptomic analysis is widely used to study human tumors. However, it remains challenging to distinguish normal cell types in the tumor microenvironment from malignant cells and to resolve clonal substructure within the tumor. To address these challenges, we developed an integrative Bayesian segmentation approach called copy number karyotyping of aneuploid tumors (CopyKAT) to estimate

Recent patents regarding the preparation, amplification and therapeutic use of circular RNA.

Recent moves of note in and around the biotech and pharma industries.

Following mixed results in the clinic against COVID-19, antibody engineers are further optimizing SARS-CoV-2 antibodies with the aim of improving outcomes.

The new drug not only is a boon for patients with spinal muscular atrophy, but also may spearhead the development of further chemical RNA modulators for a broad range of conditions.

By targeting both arms of the immune system, not just B cells, brain-penetrant inhibitors of Bruton’s tyrosine kinase could improve on anti-CD20 therapy for patients with multiple sclerosis.

Immersive virtual reality simulations tailored to aspiring industry operators in biopharma manufacturing could become a cost-effective alternative to real-life training for teaching practical skills.

Biosimilar manufacturing process patent applications first filed more than a year after the biologic is approved, which represent the largest source of patent assertions in biosimilar litigation, could be addressed without requiring intervention by either the courts or Congress.

Elucidating the volumetric architecture of organelles and molecules inside cells requires microscopy methods with a sufficiently high spatial resolution in all three dimensions. Current methods are limited by insufficient resolving power along the optical axis, long recording times and photobleaching when applied to live cell imaging. Here, we present a 3D, parallelized, reversible, saturable/switchable

Herpes simplex virus type 1 (HSV-1) is a leading cause of infectious blindness. Current treatments for HSV-1 do not eliminate the virus from the site of infection or latent reservoirs in the trigeminal ganglia. Here, we target HSV-1 genomes directly using mRNA-carrying lentiviral particles that simultaneously deliver SpCas9 mRNA and viral-gene-targeting guide RNAs (designated HSV-1-erasing lentiviral

Cell-free DNA (cfDNA) in human plasma provides access to molecular information about the pathological processes in the organs or tumors from which it originates. These DNA fragments are derived from fragmented chromatin in dying cells and retain some of the cell-of-origin histone modifications. In this study, we applied chromatin immunoprecipitation of cell-free nucleosomes carrying active chromatin

A Correction to this paper has been published: https://doi.org/10.1038/s41587-021-00813-x.

DNA point accumulation in nanoscale topography (DNA-PAINT) increases the resolution and multiplexing capabilities of super-resolution imaging, but cellular DNA interferes with DNA–DNA hybridization between target and probe in the nucleus. Here, we introduce left-handed DNA (L-DNA) oligomers that do not hybridize to natural right-handed DNA (R-DNA) and demonstrate that L-DNA-PAINT has the same specificity

Despite recent advances in metagenomic binning, reconstruction of microbial species from metagenomics data remains challenging. Here we develop variational autoencoders for metagenomic binning (VAMB), a program that uses deep variational autoencoders to encode sequence coabundance and k-mer distribution information before clustering. We show that a variational autoencoder is able to integrate these

Breeding wheat with durable resistance to the fungal pathogen Puccinia graminis f. sp. tritici (Pgt), a major threat to cereal production, is challenging due to the rapid evolution of pathogen virulence. Increased durability and broad-spectrum resistance can be achieved by introducing more than one resistance gene, but combining numerous unlinked genes by breeding is laborious. Here we generate polygenic

Current methods used for measuring amino acid side-chain reactivity lack the throughput needed to screen large chemical libraries for interactions across the proteome. Here we redesigned the workflow for activity-based protein profiling of reactive cysteine residues by using a smaller desthiobiotin-based probe, sample multiplexing, reduced protein starting amounts and software to boost data acquisition

Emergency Use Authorizations for two mRNA COVID-19 vaccines represent a turning point in the pandemic. They also herald a new era for vaccinology.

In coronavirus disease 2019 (COVID-19), hypertension and cardiovascular diseases are major risk factors for critical disease progression. However, the underlying causes and the effects of the main anti-hypertensive therapies—angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)—remain unclear. Combining clinical data (n = 144) and single-cell sequencing data of airway

Comparing diverse single-cell RNA sequencing (scRNA-seq) datasets generated by different technologies and in different laboratories remains a major challenge. Here we address the need for guidance in choosing algorithms leading to accurate biological interpretations of varied data types acquired with different platforms. Using two well-characterized cellular reference samples (breast cancer cells and

Millions of new viral sequences have been identified from metagenomes, but the quality and completeness of these sequences vary considerably. Here we present CheckV, an automated pipeline for identifying closed viral genomes, estimating the completeness of genome fragments and removing flanking host regions from integrated proviruses. CheckV estimates completeness by comparing sequences with a large

A correction to this paper has been published: https://doi.org/10.1038/s41587-020-00800-8

A Correction to this paper has been published: https://doi.org/10.1038/s41587-020-00792-5.

Generating accurate genome assemblies of large, repeat-rich human genomes has proved difficult using only long, error-prone reads, and most human genomes assembled from long reads add accurate short reads to polish the consensus sequence. Here we report an algorithm for hybrid assembly, WENGAN, that provides very high quality at low computational cost. We demonstrate de novo assembly of four human

Haplotype-resolved or phased genome assembly provides a complete picture of genomes and their complex genetic variations. However, current algorithms for phased assembly either do not generate chromosome-scale phasing or require pedigree information, which limits their application. We present a method named diploid assembly (DipAsm) that uses long, accurate reads and long-range conformation data for

Human genomes are typically assembled as consensus sequences that lack information on parental haplotypes. Here we describe a reference-free workflow for diploid de novo genome assembly that combines the chromosome-wide phasing and scaffolding capabilities of single-cell strand sequencing1,2 with continuous long-read or high-fidelity3 sequencing data. Employing this strategy, we produced a completely

Measurement of the location of molecules in tissues is essential for understanding tissue formation and function. Previously, we developed Slide-seq, a technology that enables transcriptome-wide detection of RNAs with a spatial resolution of 10 μm. Here we report Slide-seqV2, which combines improvements in library generation, bead synthesis and array indexing to reach an RNA capture efficiency ~50%

Recent patents for methods of making and using chimeric antigen receptor (CAR) T cells to treat cancer and other diseases.

The fledgling metabolic engineering industry expands its products to pest control.

Seres’s success with an industrially made bacterial mix in phase 3 trials against Clostridium difficile infection promises an alternative to fecal microbial transplantation in clinical practice.

Recent moves of note in and around the biotech and pharma industries.

The first antibody–drug conjugate to treat multiple myeloma can spur reversible loss of vision, but that may not be the case for other anti-BCMA T-cell therapies or bispecific antibodies.

Social quarantine has severely impacted the training of new scientists, but the use of virtual platforms can supplement mentorship, making career development seamless.

Cortico-striatal projections are critical components of forebrain circuitry that regulate motivated behaviors. To enable the study of the human cortico-striatal pathway and how its dysfunction leads to neuropsychiatric disease, we developed a method to convert human pluripotent stem cells into region-specific brain organoids that resemble the developing human striatum and include electrically active

Global patents in the field of CAR-T cell therapy show a changing landscape with fierce competition and intensive collaboration.

Rapid progress is being made in our understanding of RNA–protein interactions, their role in disease and their influence on the action of oligonucleotide drugs.

Nanopore sequencers can be used to selectively sequence certain DNA molecules in a pool by reversing the voltage across individual nanopores to reject specific sequences, enabling enrichment and depletion to address biological questions. Previously, we achieved this using dynamic time warping to map the signal to a reference genome, but the method required substantial computational resources and did

Human pluripotent stem cells (hPSCs) offer an unprecedented opportunity to model diverse cell types and tissues. To enable systematic exploration of the programming landscape mediated by transcription factors (TFs), we present the Human TFome, a comprehensive library containing 1,564 TF genes and 1,732 TF splice isoforms. By screening the library in three hPSC lines, we discovered 290 TFs, including

Conventional targeted sequencing methods eliminate many of the benefits of nanopore sequencing, such as the ability to accurately detect structural variants or epigenetic modifications. The ReadUntil method allows nanopore devices to selectively eject reads from pores in real time, which could enable purely computational targeted sequencing. However, this requires rapid identification of on-target

Genetic linkage causes the fate of new mutations in a population to be contingent on the genetic background on which they appear. This makes it challenging to identify how individual mutations affect fitness. To overcome this challenge, we developed marginal path likelihood (MPL), a method to infer selection from evolutionary histories that resolves genetic linkage. Validation on real and simulated

The race to bring vaccines to market is nearing the finish line. Determining which product can best contain the pandemic, however, will take more time.

A Correction to this paper has been published: https://doi.org/10.1038/s41587-019-0392-8.

Existing technologies for site-specific integration of kilobase-sized DNA sequences in bacteria are limited by low efficiency, a reliance on recombination, the need for multiple vectors, and challenges in multiplexing. To address these shortcomings, we introduce a substantially improved version of our previously reported Tn7-like transposon from Vibrio cholerae, which uses a Type I-F CRISPR–Cas system

Metabolomics using nontargeted tandem mass spectrometry can detect thousands of molecules in a biological sample. However, structural molecule annotation is limited to structures present in libraries or databases, restricting analysis and interpretation of experimental data. Here we describe CANOPUS (class assignment and ontology prediction using mass spectrometry), a computational tool for systematic

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A long-term study of AAV therapy in dogs finds clonal expansions and vector integrations.

Molecules that covalently bind macromolecular targets have found widespread applications as activity-based probes and as irreversibly binding drugs. However, the general reactivity of the electrophiles needed for covalent bond formation makes control of selectivity difficult. There is currently no rapid, unbiased screening method to identify new classes of covalent inhibitors from highly diverse pools

Nine dogs with hemophilia A were treated with adeno-associated viral (AAV) gene therapy and followed for up to 10 years. Administration of AAV8 or AAV9 vectors expressing canine factor VIII (AAV-cFVIII) corrected the FVIII deficiency to 1.9–11.3% of normal FVIII levels. In two of nine dogs, levels of FVIII activity increased gradually starting about 4 years after treatment. None of the dogs showed

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Despite early failures in the clinic, the idea of anti-aging therapies that purge the body of dying cells is gaining traction with a raft of startups now focused on senescence.

New breeding technologies accelerate germplasm improvement and reduce the cost of goods in seed production1,2,3. Many such technologies could use in vivo paternal haploid induction (HI), which occurs when double fertilization precedes maternal (egg cell) genome loss. Engineering of the essential CENTROMERIC HISTONE (CENH3) gene induces paternal HI in Arabidopsis4,5,6. Despite conservation of CENH3

The reconstruction of bacterial and archaeal genomes from shotgun metagenomes has enabled insights into the ecology and evolution of environmental and host-associated microbiomes. Here we applied this approach to >10,000 metagenomes collected from diverse habitats covering all of Earth’s continents and oceans, including metagenomes from human and animal hosts, engineered environments, and natural and

We engineered a machine learning approach, MSHub, to enable auto-deconvolution of gas chromatography–mass spectrometry (GC–MS) data. We then designed workflows to enable the community to store, process, share, annotate, compare and perform molecular networking of GC–MS data within the Global Natural Product Social (GNPS) Molecular Networking analysis platform. MSHub/GNPS performs auto-deconvolution

The imminent large-scale rollout of rapid coronavirus tests promises to aid public health responses to COVID-19 — but a rapid home test remains elusive.

A quarterly snapshot of job expansions, reductions and availability in the biotech and pharma sectors.

The prescription-only game is said to improve attention function in children with attention deficit hyperactivity disorder (ADHD).

Recent patents related to microfluidic devices and methods for single-cell analysis.

Interest in anti-inflammatory IRAK4 signaling is ramping up, as small-molecule ‘degraders’ that bind both the kinase and E3 ubiquitin ligases prepare to take on traditional kinase inhibitors.