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Related Concept Videos

Human Genetics01:28

Human Genetics

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Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
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Pleiotropy01:33

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Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
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Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
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Gregor Mendel's work (1822 - 1884) was primarily focused on pea plants. Through his initial experiments, he determined that every gene in a diploid cell has two variants called alleles inherited from each parent. He suggested that amongst these two alleles, one allele is dominant in character and the other recessive. The combination of alleles determines the phenotype of a gene in an organism.
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Genomic Imprinting and Inheritance02:30

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Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
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Expression-Driven Genetic Dependency Reveals Targets for Precision Medicine.

Abdulkadir Elmas1, Hillary M Layden2, Jacob D Ellis2

  • 1Department of Genetics and Genomic Sciences, Department of Artificial Intelligence and Human Health, Center for Transformative Disease Modeling, Tisch Cancer Institute, Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

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This study introduces BEACON, a method to find new precision oncology targets by analyzing gene expression. It identifies novel cancer targets that are essential for tumor cell survival, offering new therapeutic avenues.

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Area of Science:

  • Genomics
  • Proteomics
  • Cancer Biology

Background:

  • Cancer cells exhibit heterogeneity with diverse molecular alterations.
  • Targeted therapies based on DNA mutations are limited in tumors lacking druggable mutations.
  • New precision oncology targets are needed for patients with limited treatment options.

Purpose of the Study:

  • To identify novel precision oncology targets through expression-driven dependency.
  • To develop a computational approach for discovering genes essential for cancer cell survival based on their expression levels.
  • To create a catalog of expression-driven dependency targets for therapeutic development.

Main Methods:

  • A Bayesian approach, BEACON, was developed to analyze transcriptomic and proteomic data alongside genetic dependency profiles.
  • Data from cancer cell lines across 17 tissue lineages were jointly analyzed.
  • Experimental validation was performed for identified novel targets.

Main Results:

  • BEACON identified known druggable genes (e.g., BCL2, ERBB2, EGFR, ESR1, MYC).
  • New targets were revealed, validated by both mRNA and protein expression-driven dependency.
  • Identified genes showed significant enrichment for approved drug targets (3.8-fold) and druggable oncology targets (7-10 fold).
  • Depletion of GRHL2, TP63, and PAX5 reduced tumor cell growth and survival in dependent cells.

Conclusions:

  • Expression-driven dependency is a viable strategy for identifying novel precision oncology targets.
  • BEACON provides a powerful framework for discovering therapeutic targets in diverse cancer types.
  • The catalog of identified targets serves as a valuable resource for advancing precision oncology treatments.