Base by Base

Gustavo Barra
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  • علوم حياة
  • يتم التحديث يوميًا

Base by Base explores advances in genetics and genomics, with a focus on gene-disease associations, variant interpretation, protein structure, and insights from exome and genome sequencing. Each episode breaks down key studies and their clinical relevance—one base at a time. Powered by AI, Base by Base offers a new way to learn on the go. Special thanks to authors who publish under CC BY 4.0, making open-access science faster to share and easier to explore.

  1. قبل يوم واحد

    316: Inclusion bias in UCLA ATLAS: enrollment models, weighting, and effects on GWAS and PGS

    Pimplaskar A et al., The American Journal of Human Genetics - In UCLA ATLAS EHR-linked biobank analyses, random forest-derived enrollment probabilities and inverse-probability weighting increased replication of known GWAS variants and altered PGS associations. Study Highlights: Using the UCLA ATLAS EHR-linked biobank, the authors trained random forest classifiers on demographics, healthcare utilization, and ICD-10 features to distinguish enrolled from background patients. They converted predicted enrollment probabilities into inverse-probability weights and applied these to GWAS replication tests and PGS-PheWAS scans. The classifier achieved AUROC≈0.85 and weighting increased replication of known GWAS variants by 54% while changing phenome-wide PGS association patterns. These results indicate that enrollment-driven inclusion bias can materially affect variant discovery and downstream PGS-based phenotypic associations in health-system biobanks. Conclusion: Inclusion bias in EHR-linked biobanks like UCLA ATLAS measurably affects common-variant discovery and PGS associations, and enrollment-aware inverse-probability weighting can improve replication while reducing effective sample size. Music: Enjoy the music based on this article at the end of the episode. Reference: Pimplaskar A, Qiu J, Lapinska S, Tozzo V, Chiang JN, Pasaniuc B, Olde Loohuis LM. Inclusion bias affects common variant discovery and replication in a health-system linked biobank. The American Journal of Human Genetics. 2026;113:1–13. https://doi.org/10.1016/j.ajhg.2026.02.011 License: This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/ Support: Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/inclusion-bias-ucla-atlas

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  2. قبل ٣ أيام

    315: PLE11-encoded Rta restricts ICP1 tail assembly in Vibrio cholerae outbreaks

    Mathur Y et al., E., Monir M. M., Islam M. T., Sultana M., Ahmed T., Alam M. & Seed K. D. Capturing dynamic phage–pathogen coevolution by clinical surveillance. Nature ( - Clinical surveillance in Bangladesh shows Vibrio cholerae acquired PLE11 encoding Rta that restricts ICP1 tail assembly, driving a selective sweep of phage-resistant strains. Study Highlights: This study analysed clinical Vibrio cholerae and ICP1 isolates from stool in Bangladesh using genomic surveillance, plaque assays, qPCR, experimental phage evolution, TEM and mass spectrometry. The authors identify a newly acquired mobile element, PLE11, whose small protein Rta disrupts ICP1 tail assembly by targeting the phage tape measure protein (TMP), producing genome-filled tailless capsids. PLE11 also encodes a TMP and other tail factors enabling assembly of chimeric virions that incorporate PLE-encoded TMP and BhuB, preserving satellite transmission. Continued surveillance documented natural ICP1 counteradaptation via CRISPR–Cas acquisition and convergent TMP substitutions that restore infectivity. Conclusion: Acquisition of PLE11 encoding the tail-targeting protein Rta drove selection of phage-resistant Vibrio cholerae in Bangladesh and prompted convergent ICP1 counteradaptations that restore phage propagation. Music: Enjoy the music based on this article at the end of the episode. Reference: Mathur Y., Boyd C. M., Farnham J. E., Monir M. M., Islam M. T., Sultana M., Ahmed T., Alam M. & Seed K. D. Capturing dynamic phage–pathogen coevolution by clinical surveillance. Nature (2026). https://doi.org/10.1038/s41586-026-10136-z License: This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/ Support: Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/ple11-rta-icp1-tail-assembly

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  3. قبل ٣ أيام

    314: Proactive Genomic Reanalysis at Boston Children’s: VS-NN, HPO NLP and DRAGEN find diagnoses in pediatric ES/GS

    Rockowitz S et al., Scaling genomic reanalysis to unlock diagnoses and transform rare disease care. Human Genetics and Genomics Advances - Boston Children's Hospital used VS-NN, HPO NLP, and DRAGEN reprocessing in a proactive genomic reanalysis to identify candidate diagnoses in 2% of pediatric ES/GS cases. Study Highlights: The study deployed a centralized Proactive Genomic Reanalysis (PGR) workflow on a Boston Children’s Hospital pediatric ES/GS cohort integrated into the CRDC infrastructure. Key methods combined DRAGEN reprocessing, automated HPO extraction from EHR notes, CFA filtering on the GeneDx research platform and a VS-NN variant-scoring neural network followed by two-pass manual review. Applied to 2,144 previously unsolved cases, the pipeline flagged 310 variants, manual review prioritized 45 variants in 42 patients, and clinicians judged 33 variants to have high suspicion of disease causality, yielding ~2% candidate diagnostic rate. The work shows that institution-led, semi-automated reanalysis can produce clinically actionable findings while reducing reliance on clinician-initiated lab reanalysis, though it requires infrastructure for data transfer, confirmation and patient recontact. Conclusion: A centralized, semi-automated, clinically integrated Proactive Genomic Reanalysis workflow at Boston Children’s Hospital is feasible and identified candidate diagnostic variants in 2% of reviewed pediatric ES/GS cases, demonstrating a scalable model that can increase diagnoses while requiring institutional resources for confirmation and recontact. Music: Enjoy the music based on this article at the end of the episode. Reference: Rockowitz S, Shao W, French C, Truong TK, Hagen J, McGonigle R, et al.; and Wendy K. Chung. Scaling genomic reanalysis to unlock diagnoses and transform rare disease care. Human Genetics and Genomics Advances. 2026;7:100582. https://doi.org/10.1016/j.xhgg.2026.100582. License: This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/ Support: Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/proactive-genomic-reanalysis-bch

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  4. قبل ٥ أيام

    313: Integrating Polygenic Risk Scores and Social Determinants of Health across Populations

    Cromer SJ et al., The American Journal of Human Genetics - This paper reviews polygenic risk scores (PRS) and social determinants of health (SDoH) and outlines best practices for integrating PRS and SDoH across diverse populations to improve prediction and equity. Study Highlights: This review focuses on human populations and uses conceptual frameworks, hypothetical population examples, and synthesis of methodological studies to evaluate PRS and SDoH integration. It summarizes methods for PRS construction and transferability, SDoH measurement at individual and area levels, and analytic approaches including interaction, mediation, and calibration. Quantitatively, the authors note substantial declines in PRS predictive accuracy when applied to genetically distinct populations (for example, African-ancestry performance often ~20–40% of European-derived PRS). The review highlights harmonization, population-specific calibration, and interdisciplinary teams as functional steps to improve predictive validity and reduce inequitable impacts. Conclusion: Integrating PRSs with carefully measured and harmonized SDoH across diverse populations requires population-aware conceptual frameworks, calibrated analytic methods, diverse datasets, and ethical safeguards to improve predictive validity and equity. Music: Enjoy the music based on this article at the end of the episode. Reference: Cromer SJ, Cobran EK, Iyer HS, Hysong MR, Vargas LB, Smith JL, Konigsberg IR, Bogumil D, Glover L, King G, PRIMED Consortium SDoH Working Group, Lange LA, Patel A, Wojcik G, Raffield L, Conti DV, et al. Incorporating polygenic risk scores and social determinants of health across populations: Considerations and best practices in research. The American Journal of Human Genetics. 2026;113:1–25. https://doi.org/10.1016/j.ajhg.2026.02.007 License: This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/ Support: Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/polygenic-risk-sdoh-harmonization

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  5. قبل ٥ أيام

    312: Mfsd2a transports LPC to maintain epidermal linoleate pools and desquamation

    Wong BHH et al., PNAS - Mouse and human studies show the LPC transporter Mfsd2a enables plasma-derived LPC uptake into keratinocytes, preserving linoleate-rich phosphatidylcholine pools and promoting epidermal differentiation. Study Highlights: Using epidermis-specific (2aEpKO) and conventional (2aKO) Mfsd2a-deficient mice, lineage tracing, untargeted shotgun lipidomics, LightOx-LPC uptake assays, and primary human keratinocyte cultures, the authors mapped Mfsd2a expression to suprabasal/granular keratinocytes and demonstrated Mfsd2a-dependent uptake of plasma-derived LPC in vivo. Lipidomic quantification showed reductions in linoleate-containing phospholipids (PL-18:2 decreased ~15% in 2aEpKO and ~13% in 2aKO) and a marked loss of TAG-18:2 (−79% in 2aEpKO). Inducible epidermal Mfsd2a loss produced transient dermatitis, defective desquamation, retained lamellar bodies, and keratinocyte activation, while MFSD2A knockdown in human keratinocytes reduced LPC-driven differentiation. Functional rescue experiments in vitro revealed that LPC-18:1 and LPC-18:2 promote keratinocyte differentiation in an MFSD2A-dependent manner, linking plasma LPC uptake to epidermal lipid homeostasis and differentiation. Conclusion: Mfsd2a mediates uptake of plasma-derived LPC (notably LPC-18:2) into suprabasal keratinocytes to maintain linoleate-containing phospholipid pools and support keratinocyte differentiation and normal desquamation. Music: Enjoy the music based on this article at the end of the episode. Reference: Wong BHH, Behmoaras J, Chua AWC, Galam DLA, Tan BC, Torta F, Chin CF, Mishra K, Ding M, Silver DL. Mfsd2a is important for maintaining epidermal homeostasis. Proc. Natl. Acad. Sci. U.S.A. 2026 Feb 19;123(8):e2531159123. https://doi.org/10.1073/pnas.2531159123 License: This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/ Support: Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/mfsd2a-lpc-epidermal-homeostasis

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  6. ٨ مارس

    311: mtG3PDH (GPO1) loss in Drosophila impairs mitochondrial ATP/O, O2 consumption, and ROS

    Herpe L et al., PNAS - CRISPR knockout of Drosophila mtG3PDH (GPO1) reduces ATP production by ~60% and O2 consumption by ~33%, lowering mitochondrial efficiency and ROS emission. Study Highlights: Using CRISPR/Cas9-generated GPO1 mutant Drosophila and isolated thoracic mitochondria, the authors combined enzymatic assays, ATP production and oxygen consumption measurements, and H2O2 emission assays to probe mtG3PDH function. Loss of mtG3PDH markedly reduced mtG3PDH enzymatic activity and drove a ~60% decrease in ATP production and ~33% decrease in O2 consumption, producing a pronounced drop in mitochondrial efficiency (ATP/O). mtG3PDH-linked ROS emission was also strongly reduced (~70%), reflecting diminished direct and reverse electron-transfer ROS generation. Functionally, GPO1 flies showed sharply reduced survival and severe climbing impairment, linking the bioenergetic defects to organismal outcomes. Conclusion: mtG3PDH is essential for mitochondrial bioenergetics and redox homeostasis in Drosophila, with GPO1 loss causing major decreases in ATP production, O2 consumption, mitochondrial efficiency, and mtG3PDH-linked ROS that correlate with reduced survival and locomotion. Music: Enjoy the music based on this article at the end of the episode. Reference: Herpe L, Aminot M, Pichaud N. When alternative becomes essential: The role of mitochondrial glycerol-3-phosphate dehydrogenase. Proc. Natl. Acad. Sci. U.S.A. 2026;123(9):e2535701123. https://doi.org/10.1073/pnas.2535701123 License: This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/ Support: Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/drosophila-mtg3pdh-gpo1

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  7. ٧ مارس

    310: Infant gut microbiota restoration — maternal FMT, Bifidobacterium and Bacteroides recovery after C‑section

    Korpela K et al., Gut Microbes - Review finds maternal fecal microbiota transplantation and targeted probiotics can restore Bifidobacterium and Bacteroides after C‑section or intrapartum antibiotics, with breastfeeding aiding recovery. Study Highlights: This review focuses on term infants, particularly C‑section and intrapartum antibiotic–exposed neonates, synthesizing cohort and intervention data using 16S rRNA gene amplicon sequencing and metagenomic approaches. Maternal fecal microbiota transplantation (maternal FMT) shifted C‑section infants’ gut communities to resemble vaginally born infants and uniquely restored Bacteroidaceae, while a Bifidobacterium–Lactobacillus–FOS supplement increased bifidobacteria; vaginal seeding did not normalize overall gut composition. The authors link restoration of key taxa to potential reductions in risks such as allergy and overweight and emphasize breastfeeding as an essential adjunct to restoration strategies. Conclusion: Evidence supports action to address early-life gut microbiota disruption: probiotics and maternal FMT show promising restorative effects, but optimal, scalable solutions and long-term immune outcomes remain to be established. Music: Enjoy the music based on this article at the end of the episode. Reference: Korpela K, de Vos WM. Infant gut microbiota restoration: state of the art. Gut Microbes. 2022;14(1):e2118811. https://doi.org/10.1080/19490976.2022.2118811 License: This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/ Support: Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/maternal-fmt-bifidobacterium-restoration

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  8. ٦ مارس

    309: LASI-DAD 2,680-sample WGS panel boosts LD maps, imputation, and PRS in Indian genomes

    Li Z et al., Human Genetics and Genomics Advances. 7 ( - LASI-DAD 30× whole-genome sequencing of 2,680 Indian participants produced a 69.5M-variant LD panel that improves genotype imputation accuracy and PRS performance for Indian populations. Study Highlights: Using 30× WGS of 2,680 LASI-DAD participants, the authors constructed an LD lookup panel (69.5 million variants), phased with Eagle2.4, and identified LD structure with LDetect and Big-LD. They compared regional varLD to 1000G super-populations and evaluated imputation with Minimac4 and meta-imputation against TOPMed and GAsP. LASI-DAD increased imputation accuracy (aggregated r2) by a mean 38% versus TOPMed and 27% versus GAsP across allele frequencies and improved PRS predictive performance by 2.1%–35.1% across traits and studies. Finer-scale stronger LD and regional LD differences in LASI-DAD translate into more accurate LD estimates and better imputation and PRS transferability for Indian sub-populations. Conclusion: LASI-DAD is the largest nationally representative Indian WGS reference panel to date and it improves LD estimation, genotype imputation accuracy, and PRS construction for Indian and South Asian populations. Music: Enjoy the music based on this article at the end of the episode. Reference: Li Z, Zhao W, Zhou X, Leung YY, Schellenberg GD, Wang L-S, Schönherr S, Forer L, Fuchsberger C, Dey S, Lee J, Smith JA, Dey AB, Kardia SLR. A reference panel for linkage disequilibrium and genotype imputation using whole-genome sequencing data from 2,680 participants across India. Human Genetics and Genomics Advances. 7 (2026) 100579. https://doi.org/10.1016/j.xhgg.2026.100579. License: This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/ Support: Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/lasi-dad-india-reference-panel

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حول

Base by Base explores advances in genetics and genomics, with a focus on gene-disease associations, variant interpretation, protein structure, and insights from exome and genome sequencing. Each episode breaks down key studies and their clinical relevance—one base at a time. Powered by AI, Base by Base offers a new way to learn on the go. Special thanks to authors who publish under CC BY 4.0, making open-access science faster to share and easier to explore.

المعلومات

  • صناع العمل
    Gustavo Barra
  • سنوات النشاط
    ٢٠٢٥ - ٢٠٢٦
  • الحلقات
    ٣١٨
  • التقييم
    ملائم
  • حقوق النشر
    © Gustavo Barra
  • موقع البرنامج على الويب
    Base by Base