With 400 million individuals globally affected by rare diseases and only <5% having treatment options, the urgency for breakthroughs is clear. Elucidata, at the forefront of this revolution, offers ML-ready datasets harmonized by Polly. Our monthly roundup showcases multi-modal datasets featuring rare conditions like Duchenne muscular dystrophy, Wolf-Hirschhorn syndrome, and more. Join us in transforming the future of rare disease research. Explore with Elucidata, and let's pioneer change together.

Dataset 1

Dataset ID: GSE164891_GPL24676
Year of Publication: 2021
Disease: Bardet-Biedl Syndrome
Experiment Type: Single-cell RNA Sequencing
Total Samples: 2 (6.41k cells)
Organism: Homo sapiens
Reference Link: Publication

Why This Dataset Matters?

Unveiling Molecular Insights into Obesity and Rare Genetic Disorders like Bardet-Biedl Syndrome

Bardet-Biedl syndrome (BBS) is a rare genetic disorder that causes hyperphagic obesity. Authors in this paper created a model to study the obesity aspect of BBS using specialised brain cells generated from induced pluripotent stem cells. By analyzing the genetic activity in these cells, they discovered that certain pathways related to insulin, cAMP signaling, and nerve guidance were disrupted. The study suggests that the genetic mutations in BBS impact the way cells in the brain communicate and respond to signals related to energy balance. Fixing these genetic issues with CRISPR technology reversed some of these effects. Overall, this research provides valuable insights into how BBS affects the body's mechanisms for maintaining energy balance, particularly in the central nervous system.

This dataset is a valuable resource for researchers studying obesity and rare genetic disorders like Bardet-Biedl syndrome (BBS). It unravels the connection between gene expression and mutations. The single-cell data opens avenues for in-depth analysis of molecular pathways like KEGG, GO, and Reactome. Moreover, researchers can explore specific cell types and identify differentially expressed genes related to BBS using the pseudo-bulk method. This dataset holds promise for various analyses, contributing significantly to our understanding of rare genetic disorders and underlying molecular mechanisms.

Decoding Cell-Specific Impacts

Highlights from BBS1B Mutant Hypothalamic Neurons' Single-Cell RNA Sequencing Analysis

• Heterogeneous Neuronal Lineage: scRNA-seq confirmed the diverse nature of induced pluripotent stem cell–derived arcuate-like neurons, affirming their hypothalamic neuron lineage.
• Cell Type–Specific Effects: Differential expression analysis between BBS1B mutants and c-BBS1B (isogenic control line) controls showcased distinct impacts on various neuronal cell subtypes.
• GO and KEGG Pathway Insights:
  • Synaptic Functions: Pathway analyses were performed for genes that were either significantly up- or downregulated in BBS1B versus c-BBS1B neurons. Downregulated genes in BBS1B mutant POMC+ neurons negatively affected synaptic organization, trans-synaptic signaling, and neurogenesis.
  • Diminished Transcripts: KEGG pathways like cAMP signaling, insulin signaling, axon guidance, type 2 diabetes mellitus, and Wnt signaling pathways were significantly reduced in BBS1B mutant neurons across diverse clusters.

Conclusion

Notably, differential expression in genes tied to the cAMP signaling pathway was identified, hinting at potential connections to body weight regulation through ACIII.

Key Insights

• Heterogeneous Neurons: scRNA-seq detailed the molecular intricacies of specific neuron types, offering a nuanced view of their diverse landscape.
• Impaired Insulin Signaling: Both BBS1 and BBS10 mutant cells showed compromised insulin signaling, with scRNA-seq pinpointing reduced expression of insulin-related genes in BBS1B neurons.

Future Exploration

This dataset provides a valuable foundation for researchers to explore the implications of cAMP signaling and insulin pathway dysregulation in BBS. The diverse neuron types and affected pathways offer promising avenues for further investigations, potentially advancing therapeutic strategies for disorders like Bardet-Biedl syndrome.

Dataset 2

Dataset ID: GSE84878_GPL13112
Year of Publication: 2017
Disease: Wolf-Hirschhorn Syndrome
Experiment Type: Bulk RNA Sequencing
Total Samples: 5
Organism: Mus musculus
Reference Link: Publication

Why This Dataset Matters?

Unveiling Insights into Hematopoietic Development in Wolf-Hirschhorn Syndrome

Beyond the medical implications, rare diseases like Wolf-Hirschhorn syndrome (WHS) present a unique window to unravel crucial genes influencing development and pathology. WHS, arising from chromosome 4p arm loss, manifests severe challenges such as immunodeficiency, seizures, developmental delay, and mental retardation. Notably, the increased vulnerability to infections is a major threat to WHS patients.

This dataset, showcasing in vivo genetic evidence, provides a groundbreaking perspective on the impact of Whsc1 deficiency on hematopoietic development. The study highlights impairments at various stages and lineages, particularly affecting B cell differentiation and mature B cell function. These findings not only underscore the role of Whsc1 in hematopoietic development but also directly link reduced Whsc1 levels to immune defects associated with WHS. This dataset thus becomes a pivotal resource, shedding light on the molecular intricacies of Wolf-Hirschhorn syndrome and paving the way for potential therapeutic interventions.

Decoding Impacts

1. Differential Gene Expression Analysis:
   • RNASeq results revealed deregulation in developmental genes in the absence of the Whsc1 gene.
2. Pathway Analysis and GSEA:
   • Significant alterations in the cell cycle, splicing, ribosome synthesis, DNA replication, and repair in proliferating Whsc1−/− B cells are uncovered.
   • Emphasized downregulation of ribosomal proteins and upregulation of spliceosome and cell cycle genes, directly impacting cellular phenotypes associated with the syndrome.
   • Open Screenshot 2024-02-29 at 9.03.08 PM.png

3. Pro-B to Pre-B Cell Transition:
   1. RNA-seq Analysis:
      • Revealed deficencies in DNA repair, replication, and cell cyle gene sets in Whsc1-- pro-b cells.
   2. ‍Gene Downregulation:‍
      • Key genes for nucleosome and chromatin organization show significant downregulation.‍
4. Downregulation of Early B Cell Developmental Genes:‍
   • kzf3, Tcf3/E2a, Ebf1, Pax5, Rag1, Rag2, Il7r, and Foxo1 showed significant downregulation.
   • Indicates a vital role of Whsc1 in the specification and commitment to the B cell lineage
     

Conclusion: Unveiling Whsc1's Hematopoietic Impact

This study demonstrates Whsc1's multifaceted role in hematopoietic development, influencing stages from HSC function to B cell processes. It emerges as a central player, especially in B cell development, directly linking reduced Whsc1 levels to immune defects in Wolf-Hirschhorn Syndrome (WHS).

Key Insights

• Comprehensive Influence: Whsc1's impact spans HSC function to intricate aspects of B cell development.
• Central Regulator: Whsc1 takes a central role in orchestrating hematopoietic processes, particularly in B cell development.
• Direct Link to Immune Defects: Reduced Whsc1 levels directly correlate with immune defects in WHS, providing crucial insights into the mechanisms of immunodeficiency.

Future Exploration

These findings pave the way for future exploration. Multiple differentially expressed genes and pathways could be further explored. Also, it is possible to integrate the differential expression results from multiple public WHS rare disease datasets to unravel the insights with meta-analysis. These insights contribute to current knowledge and set the stage for continued research and therapeutic advancements in hematopoietic disorders.

Why Polly by Elucidata?

Our curated rare disease datasets, including this latest addition, are presented in a user-friendly, ready-to-use format based on meticulous ontologies and curated fields. The Polly-hosted Cellxgene platform enhances exploration, offering a seamless dive into cell types and source fields before analysis. Elevate your research with our advanced features, including pseudo-bulk analysis, data integration for multiple phenotypic datasets, and meta-analysis capabilities, providing a robust and efficient pathway to uncover molecular mechanisms. Trust in our platform for a reliable dataset and a user-friendly interface, empowering researchers to make impactful discoveries in the realm of rare diseases.

Connect with us to explore how Polly can expedite your research journey or reach us at info@elucidata.io to learn more.

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