Base by Base

Nadimpalli Kobren S et al., Nature Communications - The Undiagnosed Diseases Network (UDN) applied joint whole‑genome analysis across 4,236 individuals and introduced RaMeDiES, an analytical framework to prioritize genes by de novo recurrence and compound heterozygosity while integrating intronic splice predictions and experimental validation. The work recapitulated known diagnoses, identified new...

️ Episode 112: Local Genetic Sex Differences in Quantitative Traits In this episode of PaperCast Base by Base, we explore how genetic differences between males and females are distributed across the genome, moving beyond global averages of heritability and correlation. The study introduces a fine-scale approach using LAVA to examine local genetic sex differences across 157 quantitative traits in t...

Dörrich M et al., Nature Communications - This episode summarizes HANCOCK, a monocentric multimodal dataset of 763 head and neck cancer patients combining demographics, structured pathology and blood data, surgery reports, whole-slide images (WSIs) and tissue microarrays (TMAs). The paper demonstrates that multimodal machine learning and multiple instance learning with histopathology foundation mo...

Chick SL et al et al., Nature Communications - Largest exome-sequencing meta-analysis to date (28,898 cases, 103,041 controls, 3,444 trios) identifies STAG1 and ZNF136 at exome-wide significance and six additional genes at FDR<5%, highlighting roles for chromatin organisation and GABAergic signalling. Key terms: schizophrenia, rare coding variants, STAG1, SLC6A1, whole-exome sequencing. Study H...

️ Episode 109: Autocrine Interferon Poisoning: ADAR1–BRCA Synthetic Lethality In this episode of PaperCast Base by Base, we explore how loss of the RNA editor ADAR1 becomes lethal to BRCA1/2‑mutant cancer cells through a tumor‑cell‑autonomous interferon response, outlining a biomarker‑guided path to ADAR1‑targeted therapy. Study Highlights: A focused PRR siRNA screen and multiple orthogonal valida...

Bell HW et al et al., Nature Communications - This study shows that CpG methylation at proximal HBG promoters causally enforces perinatal silencing and that targeted epigenome editing can reverse that silencing in cell models and primary erythroblasts. UHRF1 and the methyl-CpG reader MBD2 are key mediators of repression. Key terms: HBG, CpG methylation, UHRF1, MBD2, epigenome editing. Study Highli...

Salminen A et al., Nature Communications - A large GWAS in 485,230 FinnGen participants (132,124 cases) identified genetic loci associated with pulpal and apical diseases. The study highlights strong signals near HORMAD2 on chromosome 22 and multiple signals in the HLA class II region, links top variants to immune and antigen-presentation pathways, and reports replication in independent cohorts. K...

Ecker C et al., Nature Communications - This episode reviews a study that develops a surface-based, vertex-level framework for genome-wide imaging transcriptomics using spatial interpolation of the Allen Human Brain Atlas, validates the approach against serotonergic PET maps, and applies it to dissect GABAA-receptor subunit expression and link transcriptomic signatures to cortical thickness patter...

Persi E et al., Nature Communications - This episode unpacks a multi-cohort study showing that tumors evolving toward neutral genome-level selection (dN/dS ≈ 1) during or after therapy are associated with treatment resistance and poorer outcomes. Key terms: tumor evolution, dN/dS, neutral evolution, treatment resistance, whole-exome sequencing. Study Highlights: The authors analyzed paired whole-e...

Cross-population GWAS and proteomics improve risk prediction and reveal mechanisms in atrial fibrillation Music: Enjoy the music based on this article at the end of the episode. Support: Base by Base is independent and ad-free — no sponsors, no paywall. If an episode was worth your time, chip in and keep the papers audited and the original songs coming: ❤️ Support monthly: https://buy.stripe.com/c...

Genome Sequencing Forecasts Outcomes After Congenital Cardiac Surgery Music: Enjoy the music based on this article at the end of the episode. Support: Base by Base is independent and ad-free — no sponsors, no paywall. If an episode was worth your time, chip in and keep the papers audited and the original songs coming: ❤️ Support monthly: https://buy.stripe.com/cNifZhclVebvagk2JDgEg01 ☕ One-time d...

Clinical Impact of Pharmacogenetic Risk Variants in a Large Chinese Cohort Music: Enjoy the music based on this article at the end of the episode. Support: Base by Base is independent and ad-free — no sponsors, no paywall. If an episode was worth your time, chip in and keep the papers audited and the original songs coming: ❤️ Support monthly: https://buy.stripe.com/cNifZhclVebvagk2JDgEg01 ☕ One-t...

JAK2 Inhibition Selects RAS-Mutant Clones in Myelofibrosis Music: Enjoy the music based on this article at the end of the episode. Support: Base by Base is independent and ad-free — no sponsors, no paywall. If an episode was worth your time, chip in and keep the papers audited and the original songs coming: ❤️ Support monthly: https://buy.stripe.com/cNifZhclVebvagk2JDgEg01 ☕ One-time donation: ht...

Marchi F et al., Nature Communications - This study builds the Acute Leukemia Methylome Atlas (ALMA) from 3,314 patient methylomes and presents three models—ALMA Subtype, AML Epigenomic Risk, and a 38‑CpG signature—that classify WHO2022 subtypes and predict 5‑year survival. The authors also demonstrate a nanopore-based specimen‑to‑result workflow for combined genome and epigenome profiling. Key te...

Dicke A-K et al., Nature Communications - Proteomics, molecular and genetic analyses identify NXT2 as the predominant NXT protein in the human testis that binds NXF1, NXF2 and NXF3 and associates with nucleoporins. Loss-of-function variants in NXT2 are linked to azoospermia with Sertoli cell-only testes, while an NXF3 LoF causes severe sperm defects. Key terms: NXT2, NXF3, RNA export, azoospermia,...

Busarello E et al., Nature Communications - This episode covers the Cell Marker Accordion, an integrated marker database plus R package and Shiny app that weights marker genes by specificity and evidence consistency to deliver faster, more accurate and interpretable cell-type annotations in single-cell and spatial datasets, including disease contexts. Key terms: single-cell, spatial-omics, cell-ty...

️ Episode 97: Pancreatic Cancer Genomics: Insights from the COMPASS Trial In this episode of PaperCast Base by Base, we explore how integrated whole genome and transcriptome sequencing uncovers clinically relevant subtypes and molecular features in advanced pancreatic ductal adenocarcinoma (PDAC). Study Highlights: The COMPASS trial profiled 268 advanced PDAC patients, generating whole genome and...

️ Episode 96: Early Cerebrospinal Fluid Proteomic Changes in Down Syndrome and Alzheimer’s Disease In this episode of PaperCast Base by Base, we explore a large-scale proteomic study comparing cerebrospinal fluid (CSF) profiles in individuals with Down Syndrome (DS), late-onset Alzheimer’s disease (LOAD), and autosomal dominant Alzheimer’s disease (ADAD). This study uncovers unique and shared mole...

Kubat GB et al., Nature Communications - This Perspective surveys recent biotechnological advances that enhance mitochondria transfer and transplantation (MTT) — including surface functionalization, extracellular and engineered vesicles, hydrogels and nanomotors — and evaluates their therapeutic promise and limitations across cardiac, neural and other models. Key terms: mitochondrial transplantati...

Mizuno K et al., Nature Communications - Multi-omic profiling (DNA methylation, RNA-seq, H3K27ac and H3K27me3) of 98 metastatic CRPC samples from 35 patients reveals patient-specific epigenetic signatures and methylation-driven regulation of lineage genes and therapeutic targets. Integrative analyses identify >21,000 region–gene links and highlight intraindividual heterogeneity including double...

Tipih T et al., Nature Communications - Comparative mouse study finds a dairy-cow-derived H5N1 clade 2.3.4.4b (genotype B3.13) isolate is highly virulent, producing rapid respiratory failure, systemic spread, and neurologic disease with high lung and brain viral loads and inflammatory responses. Key terms: H5N1, clade 2.3.4.4b, bovine isolate, neuroinvasion, mouse model. Study Highlights: Research...

Nature Communications - A FinnGen-based genetic and functional study identifies CFHR5 loss-of-function variants as independently protective against age-related macular degeneration and links reduced FHR-5 to altered complement activity and preserved photoreceptor structure. Key terms: CFHR5, age-related macular degeneration, FinnGen, complement system, FHR-5. Study Highlights: A GWAS and fine-mapp...

Sharapov S et al., Nature Communications - This episode examines a large multi-cohort GWAS of the human plasma N-glycome (N≈10,764) that maps genetic regulation of protein N‑glycosylation. The study doubles known glyQTLs, prioritizes candidate genes expressed in liver and lymphoid tissue, integrates glycomics, proteomics and transcriptomics, and explores links to metabolic, liver and inflammatory...

Giorgio J et al., Nature Communications - A multi-cohort neuroimaging and genetics study (n=1,354) used PET and causal path modelling to test how sex, APOE-ε4 dosage and TREM2 rare variants influence stages of the canonical amyloid→tau cascade, focusing on entorhinal (EC) and neocortical (MetaTemp) tau. Key terms: APOE-ε4, TREM2, entorhinal tau, amyloid-beta, sex differences. Study Highlights: Usi...

Förster F et al., Nature Communications - This GWAMA of up to 21,495 European-ancestry participants used the Sniffin' Sticks odour identification test to map genetic variants influencing identification of twelve odours and an identification score. The study reports ten independent loci (seven novel), sex-stratified effects, and a Mendelian randomization finding that Alzheimer's genetic risk negati...