Pesquisar referências em IA

Vamos fazer um desafio, ou seja, uma pergunta muito difícil à máquina de IA da Google (Gemma) e ao Chat-GPT.

Meta: trazer referências bibliográficas da “Doença de Gaucher” e “Experimentos de Single-Cell”

Neste momento, desconhecemos se há experimentos de Single-Cell para Gaucher, e vamos desafiar a máquina de IA Google e Chat-GPT.

Aviso

Resultado: dialogando com Chat-GPT, este foi capaz de achar uma referência! Fantástico.

Nota

Refinando a pesquisa no PubMed achamos 8 artigos, mas há vários FP!

Perguntando ao Gemma (Google)

Query: Which are the official bibliographic references for “Gaucher disease” and “Single-Cell experiments”.

Resposta

Errado, o pesquisador está errado, pois esqueci de colocar Contexto.

Aviso

Ao final do Query sempre coloque contextos aos principais termos procurado!

Refazendo a pergunta:

Query: Which are the official bibliographic references for “Gaucher disease” and “Single-Cell experiments”. Context: single-cell experiments are experiments like scRNA-seq from 10x Genomics, Illumina, and others since 2017 and Gaucher disease is an inherited metabolic disorder caused by a deficiency of the enzyme glucocerebrosidase.

Gemma: Resposta

Okay, focusing on references specifically relevant to Gaucher Disease and single-cell experiments (scRNA-seq and related technologies) since 2017, here’s a curated bibliography. This is a narrower focus than my previous response, reflecting your context. It’s still a growing field, so the number of publications is increasing rapidly.

I. Gaucher Disease & Single-Cell Experiments (2017 - Present)

These papers directly apply single-cell technologies to study Gaucher Disease pathology, cellular heterogeneity, or treatment effects.

  1. Schrimpf, C., et al. (2020). Single-cell transcriptomics reveals cellular heterogeneity and inflammatory signatures in Gaucher disease. *Blood*, *136*(18), 1988 -2001. (PMID: 32724649) - Key paper. This study used scRNA-seq to characterize the immune cell landscape in Gaucher disease patients, identifying altered inflammatory signatures and cellular proportions. A foundational study in the field.

  2. Lalazar, S., et al. (2021). Single-cell RNA sequencing reveals altered macrophage phenotypes in Gaucher disease. *Journal of Inherited Metabolic Disease*, *44*(6), 1141 -1153. (PMID: 34386814) - Focuses specifically on macrophage phenotypes in Gaucher disease using scRNA-seq, revealing dysregulation in these key cells.

  3. Gomes, A. S., et al. (2023). Single-cell transcriptomic analysis of Gaucher disease fibroblasts reveals impaired autophagy and lysosomal function. *Orphanet Journal of Rare Diseases*, *18*(1), 128. (PMID: 37038719) - Examines the impact of Gaucher disease on fibroblasts at the single-cell level, highlighting defects in autophagy and lysosomal pathways.

  4. van der Voort, R., et al. (2023). Single-cell RNA sequencing reveals distinct immune cell populations and activation states in Gaucher disease. *Molecular Genetics and Metabolism Reports*, *33*, 100819. (PMID: 37089999) - Further exploration of immune cell alterations in Gaucher disease using scRNA-seq.

  5. Bennaceur-Glaude, M., et al. (2024). Single-cell transcriptomics reveals a dysregulated immune landscape in Gaucher disease patients with splenectomy. *Scientific Reports*, *14*(1), 6883. (PMID: 38447446) - Investigates the impact of splenectomy on the immune cell composition in Gaucher disease patients using scRNA-seq.

…. <more>…

Análise da Resposta do Gemma

  1. Single-cell transcriptomics reveals cellular heterogeneity and inflammatory signatures in Gaucher disease. Blood, 136*(18), 1988 -2001. (PMID: 32724649) - **ERRADO*

  2. Single-cell RNA sequencing reveals altered macrophage phenotypes in Gaucher disease (PMID: 34386814) - ERRADO

  3. Single-cell transcriptomic analysis of Gaucher disease fibroblasts reveals impaired autophagy and lysosomal function. PMID: 37038719 - ERRADO

  4. Single-cell RNA sequencing reveals distinct immune cell populations and activation states in Gaucher disease. PMID: 37089999 ERRADO

  5. Single-cell transcriptomics reveals a dysregulated immune landscape in Gaucher disease patients with splenectomy. PMID: 38447446 - ERRADO

Todas as 5 primeiras referências estão erradas, logo o Gemma não foi capaz (até Junho de 2025) de encontrar referências.

Respondendo ao Gemma

>> unfortunately all references are wrong, but thanks

Resposta final do Gemma

You are absolutely right to call me out on that. I sincerely apologize… I am unable to reliably provide a correct bibliography at this time. I recommend using PubMed, Google Scholar, or other academic databases directly to search for the relevant literature, using the search terms I previously suggested.

Perguntando ao Chat-GPT

Query: Which are the official bibliographic references for “Gaucher disease” and “Single-Cell experiments”. Context: single-cell experiments are experiments like scRNA-seq from 10x Genomics, Illumina, and others since 2017 and Gaucher disease is an inherited metabolic disorder caused by a deficiency of the enzyme glucocerebrosidase.

Resposta

## 🧬 Gaucher Disease - 🧪 Single-Cell Experiments (scRNA-seq and Multi-Omics since 2017)

Key papers and guidelines for droplet-based and multi-omics scRNA-seq methods:

  1. Zheng GX, Terry JM, Belgrader P, et al., “Massively parallel digital transcriptional profiling of single cells.” Nat Commun. 2017;8:14049. Introduces 10x Genomics’ droplet-based scRNA-seq platform ([genomemedicine.biomedcentral.com][4]).

  2. Stoeckius M, Hafemeister C, Stephenson W, et al., “Simultaneous epitope and transcriptome measurement in single cells.” Nat Methods. 2017;14:865 -868. Landmark in multimodal CITE-seq technology ([genomebiology.biomedcentral.com][5]).

  3. Tirosh I, Izar B, Prakadan SM, et al., “Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq.” Science. 2016;352(6282):189 -196. Highly influential early application ([en.wikipedia.org][6]).

  4. Gierahn TM, et al., “Seq-Well: A Portable, Low-cost Platform for Single-Cell RNA-Seq of Low-Input Samples.” Nat Methods. 2017;14:395 -398. A key alternative platform ([en.wikipedia.org][6]).

  5. Fullgrabe A, George N, Green M, et al., “Guidelines for reporting single-cell RNA-Seq experiments.” (preprint) Oct 2019. Establishes metadata standards for reproducibility ([arxiv.org][7]).

  6. Genome Medicine: “A practical guide to single-cell RNA-sequencing for biomedical research and clinical applications.” 2017. Essential primer for scRNA-seq experimental design, platforms, QC, and analysis ([genomemedicine.biomedcentral.com][4]).

  7. Svensson V, Vento-Tormo R, Teichmann S., “Exponential scaling of single-cell RNA-seq in the last decade.” 2017 arXiv. Useful perspective on technological growth ([arxiv.org][8]).

  8. Macaulay IC, Haerty W, Kumar P, et al., “G&T-seq: Parallel sequencing of single-cell genomes and transcriptomes.” Nat Methods. 2015;12:519 -522. Demonstrates early genome+transcriptome multi-omics ([pmc.ncbi.nlm.nih.gov][9]).

### 📌 Recommended Citation List

#### For scRNA-seq & Single-Cell Methods (post-2017):

  • Zheng GX, Terry JM, Belgrader P, et al. Nat Commun. 2017;8:14049.

  • Stoeckius M, Hafemeister C, Stephenson W, et al. Nat Methods. 2017;14:865 -868.

  • Gierahn TM, et al. Nat Methods. 2017;14:395 -398.

  • Fullgrabe A, George N, Green M, et al. arXiv preprint, Oct 2019.

  • “A practical guide to single-cell RNA-sequencing…” Genome Med. 2017;9:75.

  • Svensson V, Vento-Tormo R, Teichmann S. arXiv 2017 perspective.

  • Tirosh I, et al. Science. 2016;352(6282):189-196.

  • Macaulay IC, Haerty W, Kumar P, et al. Nat Methods. 2015;12:519-522.

Análise da Resposta do Chat-GPT

ERRADO: trouxe respostas de sc-RNA-Seq mas não de Gaucher confundindo o pesquisador.

  1. “Massively parallel digital transcriptional profiling of single cells.” Nat Commun. 2017;8:14049 - ERRADO

  2. “Simultaneous epitope and transcriptome measurement in single cells.” Nat Methods. 2017;14:865 -868 - ERRADO

  3. “Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq.” Science. 2016;352(6282):189 -196 - ERRADO

  4. “Seq-Well: A Portable, Low-cost Platform for Single-Cell RNA-Seq of Low-Input Samples.” Nat Methods. 2017;14:395 -398 - ERRADO

  5. “Guidelines for reporting single-cell RNA-Seq experiments.” (preprint) Oct 2019 - ERRADO

  6. “A practical guide to single-cell RNA-sequencing for biomedical research and clinical applications.” 2017. - ERRADO

  7. “Exponential scaling of single-cell RNA-seq in the last decade.” 2017 arXiv - ERRADO

  8. “G&T-seq: Parallel sequencing of single-cell genomes and transcriptomes.” Nat Methods. 2015;12:519 -522 - ERRADO

Dialogando com Chat-GPT

Como o Chat-GPT foi mais preciso, apesar de ter confundido o pesquisador, continuamos perguntando, ou seja, dialogando. Mas, como? Além de um aplicativo de LLM ser semântico, numa dada sessão ele guarda a memória das pesquisas e respostas anteriores, permitindo o diálogo.

Dica

Em uma sessão aberta com um aplicativo de LLM, podemos dialogar com a máquina. Dialogar com um máquina faz parte do desafio de Touring. Os algoritmos anteriores eram baseados em “if-then-else” e “switch-case”, agora não há mais algoritmos. Ou seja, a máquina vai achando soluções no hiperespaço de embeddings e dialogando com o usuário, dentro de uma mesma sessão ou em uma sessão recuperada.

Query: Are there references about Gaucher Disease and Single-Cell experiments? Yes or No?

Resposta: Yes, there are references that specifically connect Gaucher disease with single-cell experiments, including single-cell RNA sequencing (scRNA-seq).

Query: I did not find any reference.

Resposta: Yes — there are studies that apply single-cell RNA sequencing to models of Gaucher disease.

Yes — there are studies that apply single-cell RNA sequencing to models of Gaucher disease.

### ✅ Examples of studies combining Gaucher disease and single-cell experiments:

  • Feldman et al., 2022 – “Gaucher Disease: Microglia orchestrate neuroinflammation” (eLife) This work uses single-cell RNA-Seq (10x Genomics + NovaSeq) in a mouse model of neuronopathic Gaucher disease to profile microglia, NK cells, astrocytes, and neurons, identifying neuroinflammatory pathways and rescue effects by targeting Gba expression ([elifesciences.org][1]).

  • Neuroinflammation in neuronopathic Gaucher disease (PMC, 2022) The study performs single-nucleus RNA-Seq with 10x Genomics, plates data through Illumina NovoSeq, and uses Seurat clustering to map cell-type–specific inflammatory signatures ([pmc.ncbi.nlm.nih.gov][2]).

### 🔍 Why these might not be obvious in standard searches:

  • They’re often categorized under transcriptomics or neuroinflammation studies rather than being indexed with both “Gaucher disease” and “single-cell” keywords.

  • Some focus on nucleus sequencing or bulk RNA, not always labeled under scRNA‑Seq in abstracts.

### ✅ Summary:

  • Yes, authoritative references exist demonstrating scRNA‑Seq of Gaucher disease models.

  • Two key studies use 10x Genomics-based single-cell platforms and uncover neuroinflammatory cell-type signatures.

I can share full citation details, DOI, or summaries of cell-type findings if you’d like!

[1]: https://elifesciences.org/articles/81890?utm_source=chatgpt.com “Gaucher Disease: Microglia orchestrate neuroinflammation | eLife” [2]: https://pmc.ncbi.nlm.nih.gov/articles/PMC9381039/?utm_source=chatgpt.com “Neuroinflammation in neuronopathic Gaucher disease: Role of microglia and NK cells, biomarkers, and response to substrate reduction therapy - PMC”

Aviso

Procurando em: “Gaucher Disease: Microglia orchestrate neuroinflammation”. ENCONTRAMOS!!! a referência correta –> ..”Boddupalli et al. found that loss of Gba1 resulted in microglia and astrocyte activation, as well as blood-derived immune cells infiltrating the brain (Figure 1A). Analyzing which genes were expressed in the different cell types of Gba1 deficient mice at a single cell resolution revealed that important neuroinflammatory networks became uncontrolled. In particular, the activated microglia expressed a set of genes that triggered an immune response. However, when the expression of Gba1 was restored in microglia, this reduced inflammation and astrocyte immune activation, stemmed the influx of immune cells, and improved mouse survival”.

Query: well done Chat-GPT, fantastic.

Resposta: Thank you! I’m really glad that helped — Gaucher disease and single-cell research is a fascinating intersection, and it’s great to see you’re digging into it deeply. If you need help interpreting the data from those studies or want to design a related experiment, just let me know!

Confirmando a referência

Nota

Referência Boddupalli CS, Nair S, Belinsky G, Gans J, Teeple E, Nguyen TH, Mehta S, Guo L, Kramer ML, Ruan J, Wang H, Davison M, Kumar D, Vidyadhara DJ, Zhang B, Klinger K, Mistry PK. Neuroinflammation in neuronopathic Gaucher disease: Role of microglia and NK cells, biomarkers, and response to substrate reduction therapy. Elife. 2022 Aug 16;11:e79830. doi: 10.7554/eLife.79830. PMID: 35972072; PMCID: PMC9381039.

Perguntando ao PubMed

  • #1: gaucher disease

  • #2: sc-rna seq

Query: #1 AND #2

Query explanation: “sc-rna”[All Fields] AND “seq”[All Fields] AND (“gaucher disease”[MeSH Terms] OR (“gaucher”[All Fields] AND “disease”[All Fields]) OR “gaucher disease”[All Fields])

Resultado

Nulo

Melhorando o Query para PubMed

  • #1: gaucher disease

  • #3: sc-rna seq OR single-cell

  • NOT flow cytomet*

Query: #1 AND #3 NOT flow cytomet*

Resposta: achou 8 artigos, mas há FP