diff --git a/README.md b/README.md index 4a05f74..3749e9a 100644 --- a/README.md +++ b/README.md @@ -13,12 +13,12 @@ $ ./papers_csv.py -a alexej.abyzov > papers.csv (III) Generate page ``` -$ python generate.py > index.html +$ python3 generate.py > index.html ``` (IV) Test ``` -$ python -m SimpleHTTPServer +$ python3 -m SimpleHTTPServer ``` Then open in broser [web page](localhost:8000) diff --git a/index.html b/index.html index a623c68..d1c8231 100644 --- a/index.html +++ b/index.html @@ -1,4 +1,4 @@ - + Abyzov Lab @@ -191,7 +191,7 @@ @@ -274,6 +274,22 @@

Analysis of mosaic variations in human

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Publication from the lab in Nature Neuroscience

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+ Modeling idiopathic autism in forebrain organoids reveals an imbalance of excitatory cortical neuron subtypes during early neurogenesis
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Idiopathic autism spectrum disorder (ASD) is highly heterogeneous, and it remains unclear how convergent biological processes in affected individuals may give rise to symptoms. Here, using cortical organoids and single-cell transcriptomics, we modeled alterations in the forebrain development between boys with idiopathic ASD and their unaffected fathers in 13 families. Transcriptomic changes suggest that ASD pathogenesis in macrocephalic and normocephalic probands involves an opposite disruption of the balance between excitatory neurons of the dorsal cortical plate and other lineages such as early-generated neurons from the putative preplate. The imbalance stemmed from divergent expression of transcription factors driving cell fate during early cortical development. While we did not find genomic variants in probands that explained the observed transcriptomic alterations, a significant overlap between altered transcripts and reported ASD risk genes affected by rare variants suggests a degree of gene convergence between rare forms of ASD and the developmental transcriptome in idiopathic ASD.
+ More: https://www.nature.com/articles/s41593-023-01399-0
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posted August 19, 2023 by Alexej Abyzov
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Publication from the lab in The CRISPR Journal

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posted April 11, 2023 by Alexej Abyzov
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Publication from the lab in Science

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- Analysis of somatic mutations in 131 human brains reveals aging-associated hypermutability
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We analyzed 131 human brains (44 neurotypical, 19 with Tourette syndrome, 9 with schizophrenia, and 59 with autism) for somatic mutations after whole genome sequencing to a depth of more than 200×. Typically, brains had 20 to 60 detectable single-nucleotide mutations, but ~6% of brains harbored hundreds of somatic mutations. Hypermutability was associated with age and damaging mutations in genes implicated in cancers and, in some brains, reflected in vivo clonal expansions. Somatic duplications, likely arising during development, were found in ~5% of normal and diseased brains, reflecting background mutagenesis. Brains with autism were associated with mutations creating putative transcription factor binding motifs in enhancer-like regions in the developing brain. The top-ranked affected motifs corresponded to MEIS (myeloid ectopic viral integration site) transcription factors, suggesting a potential link between their involvement in gene regulation and autism.
- More: https://www.science.org/doi/10.1126/science.abm6222
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diff --git a/news.csv b/news.csv index 6e500c7..8c7945f 100644 --- a/news.csv +++ b/news.csv @@ -1,3 +1,4 @@ +Publication from the lab in Nature Neuroscience;https://www.nature.com/articles/s41593-023-01399-0;;Modeling idiopathic autism in forebrain organoids reveals an imbalance of excitatory cortical neuron subtypes during early neurogenesis;posted August 19, 2023 by Alexej Abyzov;Idiopathic autism spectrum disorder (ASD) is highly heterogeneous, and it remains unclear how convergent biological processes in affected individuals may give rise to symptoms. Here, using cortical organoids and single-cell transcriptomics, we modeled alterations in the forebrain development between boys with idiopathic ASD and their unaffected fathers in 13 families. Transcriptomic changes suggest that ASD pathogenesis in macrocephalic and normocephalic probands involves an opposite disruption of the balance between excitatory neurons of the dorsal cortical plate and other lineages such as early-generated neurons from the putative preplate. The imbalance stemmed from divergent expression of transcription factors driving cell fate during early cortical development. While we did not find genomic variants in probands that explained the observed transcriptomic alterations, a significant overlap between altered transcripts and reported ASD risk genes affected by rare variants suggests a degree of gene convergence between rare forms of ASD and the developmental transcriptome in idiopathic ASD. Publication from the lab in The CRISPR Journal;https://www.liebertpub.com/doi/10.1089/crispr.2022.0050;;Clonally Selected Lines After CRISPR-Cas Editing Are Not Isogenic;posted June 14, 2023 by Alexej Abyzov;The CRISPR-Cas9 system has enabled researchers to precisely modify/edit the sequence of a genome. A typical editing experiment consists of two steps: (1) editing cultured cells, (2) cell cloning and selection of clones with and without intended edit, presumed to be isogenic. The application of CRISPR-Cas9 system may result in off-target edits, whereas cloning will reveal culture-acquired mutations. We analyzed the extent of the former and the latter by whole genome sequencing in three experiments involving separate genomic loci and conducted by three independent laboratories. In all experiments we hardly found any off-target edits, whereas detecting hundreds to thousands of single nucleotide mutations unique to each clone after relatively short culture of 10-20 passages. Notably, clones also differed in copy number alterations (CNAs) that were several kb to several mb in size and represented the largest source of genomic divergence among clones. We suggest that screening of clones for mutations and CNAs acquired in culture is a necessary step to allow correct interpretation of DNA editing experiments. Furthermore, since culture associated mutations are inevitable, we propose that experiments involving derivation of clonal lines should compare a mix of multiple unedited lines and a mix of multiple edited lines. We are part of SMaHT network established by NIH Common Fund Program;https://www.nih.gov/news-events/news-releases/nih-launches-140-million-effort-investigate-genetic-variation-normal-human-cells-tissues;;NIH launches $140 million effort to investigate genetic variation in normal human cells and tissues. Common Fund Program will accelerate research on human development, aging, and disease.;posted May 11, 2023 by Alexej Abyzov; Publication from the lab in Nucleic Acid Research;https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkad254/7110756;;Efficient reconstruction of cell lineage trees for cell ancestry and cancer;posted April 11, 2023 by Alexej Abyzov;Mosaic mutations can be used to track cell ancestries and reconstruct high-resolution lineage trees during cancer progression and during development, starting from the first cell divisions of the zygote. However, this approach requires sampling and analyzing the genomes of multiple cells, which can be redundant in lineage representation, limiting the scalability of the approach. We describe a strategy for cost- and time-efficient lineage reconstruction using clonal induced pluripotent stem cell lines from human skin fibroblasts. The approach leverages shallow sequencing coverage to assess the clonality of the lines, clusters redundant lines and sums their coverage to accurately discover mutations in the corresponding lineages. Only a fraction of lines needs to be sequenced to high coverage. We demonstrate the effectiveness of this approach for reconstructing lineage trees during development and in hematologic malignancies. We discuss and propose an optimal experimental design for reconstructing lineage trees.