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Clinical studies have demonstrated that the composition of the gut microbiome often links to patient health. However, recent work has also revealed extensive variation in the composition of the gut microbiome, even among seemingly healthy patients. In this issue of Nature Medicine, two large-scale clinical microbiome studies provide transformative insight into two factors contributing to this variation: ethnicity and geography. The cover art is a conceptual representation of the work by Hong-wei Zhou and colleagues identifying host location as having the strongest association with microbiota variation in a cohort of 7,009 individuals from 14 districts within a single province in China.
Thanks to improvements in data collection and analysis, some polygenic risk scores that predict disease risk are approaching the same predictive accuracy offered by tests for monogenic mutations. The time to think about how best to incorporate polygenic tests in the clinic is now.
Acquired resistance to CD19-targeted CAR T cell therapy can occur through mutations in the CD19 gene or after insertion of a chimeric antigen receptor (CAR) into leukemia cells, resulting in the adjacent receptor being masked by the CAR.
The taxonomic composition of the gut microbiome associates with patient ethnicity and geographic location. This association impacts the development of microbiome-based applications for personalized medicine.
A CAR gene unintentionally introduced in a contaminating leukemia cell during the manufacturing of CAR T cells caused a patient to relapse after therapy.
Mutations in the CD19 gene suggesting irreversible loss of its surface expression are identified in the majority of analyzed cases of CD19– relapse in two clinical trials of pediatric ALL CD19 CAR T therapy, offering considerations for the rational choice of follow-up therapies.
The long-term follow-up results of a phase 1/2 retinal gene therapy clinical trial for choroideremia (NCT01461213) support the safety and efficacy of the treatment.
AAV-mediated base editing corrects an autosomal recessive mutation in the Pahenu2 gene and ameliorates molecular deficits in a mouse model of metabolic liver disease.
Stool microbiota composition correlates with the ethnic backgrounds of people living in the same city, suggesting that geographical location and ethnicity have distinct effects on microbiota.
Large tumors induce anemia and expansion of CD45+ immature erythroid cells, which represent a major immunosuppressive population in the spleen, contributing to systemic suppression of T cell immunity in late-stage cancer.
A gene signature identified in spontaneously regressing neuroblastoma identifies responders to immune checkpoint blockade among patients with melanoma with accuracy superior to previously reported biomarkers.
An algorithm-selected gene signature focused on tumor immune evasion and suppression predicts response to immune checkpoint blockade in melanoma, exceeding the accuracy of current clinical biomarkers.
A convolutional neural network model using feature extraction and machine-learning techniques provides a tool for classification of lung cancer histopathology images and predicting mutational status of driver oncogenes
CRISPR–Cas9-mediated gene editing of TSC1 and TSC2 in human pluripotent stem cells is used to investigate the contribution of tuberous sclerosis complex–mechanistic target of rapamycin complex 1 signaling to human neural development in two-dimensional monolayer and three-dimensional spheroid models of the neurodevelopmental disorder tuberous sclerosis complex.
iPSC-derived motor neurons from over 30 heterogeneous sporadic ALS cases exhibit pathologies correlated with clinical disease progression, are more similar to FUS/TDP-43 familial ALS than SOD1-ALS and are corrected by repurposing of ropinirole.
Distinct routes of immunization elicit different antibody isotypes and functions associated with protection against SIV infection that converge on phagocytosis as a candidate protective mechanism of independent SIV vaccines.
In-depth methylation analysis of formalin-fixed paraffin-embedded glioblastoma samples demonstrates heterogeneity between primary and recurring tumors and enables prediction of composition of the tumor microenvironment and insights into progression.