Base by Base

🎙️ Episode 92: Genetic Loss of CFHR5 Function Protects Against Age-Related Macular Degeneration

🧬 In this episode of PaperCast Base by Base, we explore a genome‑wide association and fine‑mapping study in a Finnish cohort that identifies CFHR5 loss‑of‑function variants as independent protective factors against age‑related macular degeneration and investigates their impact on complement activation and retinal structure.

🔍 Study High...

🎙️ Episode 91: Genome-wide Association of Plasma N-Glycome Reveals Links to Liver Disease and Anti-Inflammatory Proteins

🧬 In this episode of PaperCast Base by Base, we explore a large-scale genome-wide association study that uncovers novel genetic regulators of plasma protein N-glycosylation and their connections to liver function and inflammatory pathways.

🔍 Study Highlights:

We conducted a meta-analysis of genome-wide associatio...

🎙️ Episode 90: Variable and Interactive Effects of Sex, APOE ε4 and TREM2 on Tau Deposition

🧬 In this episode of PaperCast Base by Base, we explore how genetic factors—including sex differences, Apolipoprotein E ε4 allele dosage, and rare TREM2 risk variants—shape the accumulation and spread of tau pathology in Alzheimer’s disease using multimodal imaging and causal path analysis.

🔍 Study Highlights:

This multi-cohort investiga...

🎙️ Episode 89: Decoding the Genetics of Smell: Sex-Specific Variants in Olfactory Identification

🧬 In this episode of PaperCast Base by Base, we explore how a genome-wide association meta-analysis of olfactory identification across 21,495 individuals reveals novel genetic loci underlying human smell perception.

🔍 Study Highlights:

Using the Sniffin’ Sticks screening test across four European cohorts totaling 21,495 individuals, the...

🎙️ Episode 88: Stable Heritability of Type 1 Diabetes Over Three Decades in Sweden

🧬 In this episode of PaperCast Base by Base, we explore a Swedish nationwide register-based study that assesses whether the heritability of childhood-onset type 1 diabetes has changed from 1982 to 2010 and how environmental factors have contributed to the rising incidence.

🔍 Study Highlights:

Leveraging data from nearly three million children bor...

🎙️ Episode 87: Circulating cfDNA Methylation Reveals Allograft Injury Sources after Liver Transplant

🧬 In this episode of PaperCast Base by Base, we explore how sequence-based analysis of cell-free DNA methylation patterns can non-invasively monitor and differentiate cellular sources of allograft injury in liver transplant patients within the first post-operative month.

🔍 Study Highlights:

The authors performed hybridization captur...

🎙️ Episode 86: Variable Penetrance in Monogenic Traits — How Genetic Background Modulates Disease Severity

🧬 In this episode of PaperCast Base by Base, we explore a landmark study that unravels why carriers of the same pathogenic variant often present with very different clinical outcomes, providing new insights into gene–disease association, variant interpretation, and the interplay between rare and common genetic effects.

🔍 Stud...

🎙️ Episode 85: Genomic landscape of virus-associated cancers

🧬 In this episode of PaperCast Base by Base, we explore the comparative genomic analysis of virus-positive and virus-negative tumors across nine cancer types linked to five oncogenic viruses uncovering epidemiological patterns, mutational signatures, and therapeutic implications.

🔍 Study Highlights:

The authors aggregated genomic data from 1,971 tumors spanning nine virus...

🎙️ Episode 84: Variants in NR6A1 cause a novel oculo-vertebral-renal syndrome

🧬 In this episode of PaperCast Base by Base, we explore the discovery of rare variants in the orphan nuclear receptor gene NR6A1 as the genetic cause of a newly described autosomal dominant oculo-vertebral-renal (OVR) syndrome characterized by colobomatous microphthalmia, vertebral anomalies, and congenital kidney abnormalities.

🔍 Study Highlights:

We per...

🎙️ Episode 83: Single-cell Analysis of dup15q Syndrome Illuminates Autism Mechanisms

🧬 In this episode of PaperCast Base by Base, we explore how single-cell RNA sequencing of patient-derived cortical organoids and postmortem brain tissue uncovers developmental and postnatal molecular changes in duplication 15q syndrome, a major genetic cause of autism.

🔍 Study Highlights:

The authors performed single-cell and single-nucleus transcr...

🎙️ Episode 82: JAK2 Inhibition Drives RAS Pathway Mutant Clonal Selection in Myeloproliferative Neoplasms

🧬 In this episode of PaperCast Base by Base, we explore how JAK2 inhibition by ruxolitinib reshapes clonal dynamics in myelofibrosis by mediating the expansion of RAS pathway-mutated clones in myeloproliferative neoplasms.

🔍 Study Highlights:

We conducted a longitudinal molecular analysis of myelofibrosis patients treated with ...

🎙️ Episode 81: Clinical Impact of Pharmacogenetic Risk Variants in a Large Chinese Cohort

🧬 In this episode of PaperCast Base by Base, we explore a retrospective analysis of genetic and clinical data from the Taiwan Precision Medicine Initiative cohort to assess how actionable pharmacogenetic variants influence drug response and adverse events in nearly half a million Han Chinese individuals.

🔍 Study Highlights:

We performed a comp...

🎙️ Episode 80: Genomic Forecasting of Postoperative Outcomes in Congenital Cardiac Surgery

🧬 In this episode of PaperCast Base by Base, we explore the use of artificial intelligence–driven genome sequencing to predict clinical outcomes following surgery for congenital heart defects.

🔍 Study Highlights:

The authors conducted a prospective observational cohort study of 2,253 patients from the Pediatric Cardiac Genomics Consortium, in...

🎙️ Episode 79: Cross-Population GWAS and Proteomic Insights in Atrial Fibrillation

🧬 In this episode of PaperCast Base by Base, we explore a cross-population genome-wide meta-analysis combined with proteomic profiling to enhance risk prediction and uncover molecular mechanisms underlying atrial fibrillation.

🔍 Study Highlights:

The authors conducted a meta-analysis of over 168,000 atrial fibrillation cases across diverse ancestries...

🎙️ Episode 78: Interactions between TTYH2 and APOE Facilitate Endosomal Lipid Transfer

🧬 In this episode of PaperCast Base by Base, we explore the discovery and characterization of the interaction between the membrane protein TTYH2 and apolipoprotein E (APOE), and how this partnership drives lipid transfer within endosomal compartments.

🔍 Study Highlights:

Pull-down assays and mass spectrometry identified APOE as a binding partner ...

🎙️ Episode 77: Range Extender: Unlocking Long-Distance Enhancer Activity

🧬 In this episode of PaperCast Base by Base, we explore the discovery and functional characterization of a novel cis-acting element, termed REX, that mediates megabase-scale enhancer–promoter interactions and enables remote gene activation during limb development.

🔍 Study Highlights:

The authors performed in vivo enhancer-replacement experiments at the mouse S...

🎙️ Episode 76: Whole-genome Ancestry of an Old Kingdom Egyptian

🧬 In this episode of PaperCast Base by Base, we explore the first 2× coverage whole-genome sequence recovered from a high-status individual of the Old Kingdom excavated at the Nuwayrat necropolis and examine the evidence for multi-regional ancestry during early Dynastic Egypt.

🔍 Study Highlights:

The research team extracted and authenticated ancient DNA from a pot-buri...

🎙️ Episode 75: Metabolic Shaping of Enzyme Structures Over 400 Million Years

🧬 In this episode of PaperCast Base by Base, we explore a large-scale study published in Nature by Lemke et al. that leverages AlphaFold2-predicted and experimentally determined enzyme structures across 27 yeast species to reveal how metabolic properties have constrained and shaped enzyme structural evolution over 400 million years in the Saccharomycotina...

🎙️ Episode 74: Benchmarking T Cell Receptor–Epitope Predictors with ePytope-TCR
🧬 In this episode of PaperCast Base by Base, we explore a unified computational framework that integrates and benchmarks 21 T cell receptor–epitope binding prediction models to evaluate their performance on viral epitope repertoires and deep mutational scans.
🔍 Study Highlights:
The authors developed ePytope-TCR, which standardizes 18 genera...