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This Resource describes data, code and tools developed for the Human Reference Atlas and the Human BioMolecular Atlas Program for building and navigating a multiscale human atlas.

The bacterial Tad pilus extends and retracts using a single bifunctional ATPase CpaF. Here, the authors employ cryo-EM, fluorescent microscopy, and AlphaFold modelling to propose how a rotary mechanism of CpaF catalysis drives Tad pilus assembly.

The Cancer Genome Atlas Research Network reports an integrative analysis of more than 400 samples of clear cell renal cell carcinoma based on genomic, DNA methylation, RNA and proteomic characterisation; frequent mutations were identified in the PI(3)K/AKT pathway, suggesting this pathway might be a potential therapeutic target, among the findings is also a demonstration of metabolic remodelling which correlates with tumour stage and severity.

An integrated transcriptome, genome, methylome and proteome analysis of over 200 lung adenocarcinomas reveals high rates of somatic mutations, 18 statistically significantly mutated genes including RIT1 and MGA, splicing changes, and alterations in MAPK and PI(3)K pathway activity.

Safely opening university campuses has been a major challenge during the COVID-19 pandemic. Here, the authors describe a program of public health measures employed at a university in the United States which, combined with other non-pharmaceutical interventions, allowed the university to stay open in fall 2020 with limited evidence of transmission.

Pathologic α-synuclein spreads from cell-to-cell through binding to the lymphocyteactivation gene 3 (Lag3). Here, the authors demonstrate that the amyloid β precursor-like protein 1 (Aplp1) interacts with Lag3 and facilitates the binding, internalization, transmission, and toxicity of pathologic α-synuclein.

Studies show the cancer transcriptome correlates poorly with the cancer proteome, questioning the role of chromatin regulation. Here the authors demonstrate proximal-gene-body chromatin elements and transcription predict abundances of differentially expressed proteins in thyroid and breast cancers.

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

Systematic characterization of longitudinal tau variability in human Alzheimer’s disease using an unbiased subtyping algorithm reveals four trajectories of tau deposition with distinct clinical features.

Personalized omics profiling can lead to actionable health discoveries and stimulate lifestyle changes.

Diagnosis of lung cancer through manual histopathology evaluation is insufficient to predict patient survival. Here, the authors use computerized image processing to identify diagnostically relevant image features and use these features to distinguish lung cancer patients with different prognoses.

Bramel et al. identify a population of GATA4⁺ vascular smooth muscle cells enriched in the human and mouse aortic root that is intrinsically more susceptible to Loeys–Dietz-syndrome-causing mutations and demonstrate that postnatal deletion of Gata4 in vascular smooth muscle cells reduces aortic root dilation in a mouse model of Loeys–Dietz syndrome.

In a large, partially prospective cohort of patients with molecularly profiled and clinically annotated meningioma, the extent of surgical resection and radiotherapy (RT) response correlate with molecular classification, which can be used in a molecular model to predict clinical outcomes in response to RT.

The interplay between amyloid and tau pathology in Alzheimer’s disease is still not well understood. Here, the authors show that amyloid-related increased in soluble p-tau is related to subsequent accumulation of tau aggregates and cognitive decline in early stage of the disease.

The BIN1 SNP rs744373 is associated with higher CSF tau and phosphorylated tau levels. Here the authors show, using PET imaging, that this SNP is associated with tau accumulation in the brain as well as impaired memory in older individuals without dementia.

Here the authors studied pulmonary arterial endothelial cells (PAEC) under laminar shear stress and show that this physiologic condition markedly changes chromatin accessibility at regulatory regions, when compared to cells grown in a static state. They find that KLF4 organizes chromatin by interacting with the SWI/SNF nucleosome remodeling complex to regulate vasculo-protective gene expression.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

In Alzheimer’s disease (AD) tau and neurodegeneration have complex regional relationships. Here, the authors show neuronal hypometabolism discordant with tau burden defines functional resilience or susceptibility to Alzheimer’s pathology via limbic/cortical axes. Susceptible groups have faster cognitive decline and evidence of non-Alzheimer’s pathologies.

Longitudinal deep lipidome profiling reveals >800 lipid species, many of which are associated with health-to-disease transitions in diabetes, ageing and inflammation.

Whether Alzheimer’s disease originates in basal forebrain or entorhinal cortex remains highly debated. Here the authors use structural magnetic resonance data from a longitudinal sample of participants stratified by cerebrospinal biomarker and clinical diagnosis to show that tissue volume changes appear earlier in the basal forebrain than in the entorhinal cortex.

Late-onset Alzheimer's disease (LOAD) is a complex multi-factorial disorder. Here, the authors perform a data-driven analysis of LOAD progression, including multimodal brain imaging, plasma and CSF biomarkers, and find vascular dysfunction is among the earliest and strongest altered events.

Brain-iron elevation is implicated in Alzheimer’s disease (AD), but the impact of the metal on disease outcomes has not been analysed in a longitudinal study. Here, the authors examine the association between the levels of ferritin, an iron storage protein, in the cerebrospinal fluid (CSF) of AD patients and show that CSF ferritin levels predict AD outcomes.

Michael Snyder and colleagues analyze whole-genome sequencing data from eight cancer subtypes and identify recurrent mutations in regulatory regions. They find evidence for positive selection of mutations in transcription factor binding sites near cancer-related genes.

An integrative genomic analysis of several hundred endometrial carcinomas shows that a minority of tumour samples carry copy number alterations or TP53 mutations and many contain key cancer-related gene mutations, such as those involved in canonical pathways and chromatin remodelling; a reclassification of endometrial tumours into four distinct types is proposed, which may have an effect on patient treatment regimes.

Understanding the molecular changes underlying aging is important for developing biomarkers and healthy aging interventions. In this study, the authors used comprehensive multi-omics data to reveal nonlinear molecular profiles across chronological ages, highlighting two substantial variations observed around ages 40 and 60, which are linked to increased disease risks.

An atlas explores the landscape of recurrent repeat expansions in human cancer genomes.

Dense multi-omics microsampling for the frequent capture and analysis of thousands of molecules in blood alongside physiological information from wearables facilitates the profiling of lifestyle-associated changes in an individual’s health.

A wireless ‘smart’ bandage stimulates wound healing.

Off-target effects in CRISPR screens for essential regulatory elements have not been systematically evaluated. Here the authors find Cas9 nuclease, CRISPRi/a each have distinct off-target effects, and that these can be accurately identified and removed using the GuideScan sgRNA specificity score.

Eight genome-wide CRISPR screens identify genes required for substrate-specific phagocytosis. The study highlights roles for NHLRC2 in filopodia formation, very-long-chain fatty acids in substrate-specific phagocytosis and TM2D3 in uptake of amyloid-β aggregates.

ENCODE is a resource comprising thousands of functional genomic datasets. Here, the authors present custom annotation within ENCODE for cancer, highlighting a workflow that can help prioritise key elements in oncogenesis.

Pamela Sklar, Chair of the Department of Genetics and Genomic Sciences and endowed Professor of Psychiatric Genetics at the Icahn School of Medicine at Mount Sinai in New York City, died 20 November 2017 after a long illness.

Primary lymphoedema can lead to the swelling of the extremities and facial dysmorphism. Here the authors present evidence that compound heterozygous and homozygous mutations inPIEZO1result in an autosomal recessive form of generalised lymphatic dysplasia.

The KL-VS haplotype of the Klotho gene has been associated with reduced risk of Alzheimer’s disease and dementia. Here the authors show an association between the KL-VS haplotype and amyloid-dependent tau accumulation using PET data.

Snyder et al. report that hippocampal neurons in Egyptian fruit bats modulate their activity depending on the position and identity of human experimenters when bats are flying and encode experimenter position and identity when bats are stationary.

Sun et al. report human lifespan changes in the brain’s functional connectome in 33,250 individuals, which highlights critical growth milestones and distinct maturation patterns and offers a normative reference for development, aging and diseases.

Bahmani, Cha, Alavi, Dixit et al. evaluate an AI-facilitated precision medicine learning platform they built, Stanford Data Ocean. The platform, which provided 3594 costfree certification accesses across 93 countries, demonstrates positive training outcomes across bioinformatics topics for low and middle income learners.

Pathogenesis of neurodevelopmental delays in infants during maternal Zika virus infection is not well understood. Here, the authors show that congenital Zika virus infection in macaques disrupts fetal neurodevelopment through myelin decompaction and suppression of myelin gene expression.

A description is given of the ENCODE consortium’s efforts to examine the principles of human transcriptional regulatory networks; the results are integrated with other genomic information to form a hierarchical meta-network where different levels have distinct properties.

Human leukocyte antigen loss of heterozygosity (HLA LOH) is an important mechanism of immune escape in patients with cancer. Here the authors design and validate a machine learning algorithm with subclonal sensitivity for the identification of HLA LOH from paired tumor-normal sequencing data.