Neel
Roy
Deep Learning Framework for Genetic Perturbation Response Prediction
Abstract profile. Full document pending author claim.
Authors:
Neel Roy, Omar Abudayyeh, Jonathan Gootenberg
Date Created:
2025-01-01
Course Title:
Professor:
Not specified
About Paper:
Accurate prediction of cellular responses to genetic perturbations expression fold changes. We validate the model on CRISPR is critical for understanding gene function and guiding therapeuticperturbations in multiple cell types and recover known regulatory development. Here, we present a computational framework that relationships. Our framework provides an interpretable and integrates genetic and perturbation embeddings with machine scalable approach to predict cellular responses, paving the way learning to predict gene expression changes measured by single- for insilico screeningofgenetargetsandpersonalizedperturbation cell RNA sequencing following perturbation. We simulate experiments. We further develop a method for creating synthetic perturbations in silico by applying mean shifts to synthetic singlesingle-cellsequencingdatafrombulkRNAsequencingdata,which cell profiles and train a model to learn cascading effects across can be used for future experimentation. Our results demonstrate genes in the cell. The model uses a zero-shot prediction improved predictive accuracy and robust interpretability. This architecture to generalize to unseen perturbations and cell types, strategy provides a versatile platform to inform experimental achieving high correlation between predicted and observed gene perturbation study design. 124 Program for Research in Science and Engineering Determining Factors Mediating in vitro Chondrocyte to Osteoblast Transdifferentiation Mia Russ, Tim Hammersen, April Craft Harvard College | Lowell House | Human Developmental and Regenerative Biology | 2026 37% of adults have a degenerative cartilage disease. Today, Enhanced hypertrophy was induced using an Indian Hedgehog patients are offered Autologous Chondrocyte Implantation, Pathway activator or thyroid hormone. Phosphate was added wherein cartilage is replaced with patient cells, however to tissues to induce mineralization of the Type X Collagen this cartilage does not contain the gradient of layers in matrix. Wnt activators were added to induce chondrocyte to native cartilage and often fails to integrate into host tissue. osteoblast transdifferentiation. Hypertrophy and mineralization Stem cell-based cartilage offers a promising alternative. In was quantified using RT-qPCR for COL10 expression and development, mesenchymal stem cells become chondrocytes and visualized through histological analysis for Type X Collagen, transdifferentiate into bone through endochondral ossification. glycosaminoglycan, and alkaline phosphatase (ALP). Preliminary Through directed differentiation, induced pluripotent stem cellsresults indicate Indian Hedgehog Pathway activation increased (iPSCs) may develop into chondrocytes and then transdifferentiatehe number of hypertrophic chondrocytes but degraded tissue into bone, generating a tissue containing bone and cartilage. integrity, reducing glycosaminoglycans. Thyroid hormone We aim to optimize this process by determining factors enhanced hypertrophy by increasing hypertrophic chondrocytes required to transition chondrocytes into osteoblasts. We and increasing glycosaminoglycan production. Phosphate hypothesized that by enhancing hypertrophy, supplementing supplementation mineralized the tissue matrix after eight weeks with phosphate, and activating Wnt signalling, iPSC-derived of BMP-4 treatment, as indicated by ALP staining. RT- hypertrophic chondrocytes will develop a robust and mineralized qPCR and Wnt signaling results are forthcoming.This study Type X Collagen matrix, and hypertrophic chondrocytes provides preliminary insights into an iPSC-derived endochondral will transdifferentiate into osteoblasts. Human iPSCs were ossification model that may generate cartilage-bone tissue differentiated into hypertrophic chondrocytes via TGF-β treatmentonstructs for treating degenerative cartilage diseases. (2 weeks) followed by BMP-4 treatment (up to 12 weeks).
Abstract:
Accurate prediction of cellular responses to genetic perturbations expression fold changes. We validate the model on CRISPR is critical for understanding gene function and guiding therapeuticperturbations in multiple cell types and recover known regulatory development. Here, we present a computational framework that relationships. Our framework provides an interpretable and integrates genetic and perturbation embeddings with machine scalable approach to predict cellular responses, paving the way learning to predict gene expression changes measured by single- for insilico screeningofgenetargetsandpersonalizedperturbation cell RNA sequencing following perturbation. We simulate experiments. We further develop a method for creating synthetic perturbations in silico by applying mean shifts to synthetic singlesingle-cellsequencingdatafrombulkRNAsequencingdata,which cell profiles and train a model to learn cascading effects across can be used for future experimentation. Our results demonstrate genes in the cell. The model uses a zero-shot prediction improved predictive accuracy and robust interpretability. This architecture to generalize to unseen perturbations and cell types, strategy provides a versatile platform to inform experimental achieving high correlation between predicted and observed gene perturbation study design. 124 Program for Research in Science and Engineering Determining Factors Mediating in vitro Chondrocyte to Osteoblast Transdifferentiation Mia Russ, Tim Hammersen, April Craft Harvard College | Lowell House | Human Developmental and Regenerative Biology | 2026 37% of adults have a degenerative cartilage disease. Today, Enhanced hypertrophy was induced using an Indian Hedgehog patients are offered Autologous Chondrocyte Implantation, Pathway activator or thyroid hormone. Phosphate was added wherein cartilage is replaced with patient cells, however to tissues to induce mineralization of the Type X Collagen this cartilage does not contain the gradient of layers in matrix. Wnt activators were added to induce chondrocyte to native cartilage and often fails to integrate into host tissue. osteoblast transdifferentiation. Hypertrophy and mineralization Stem cell-based cartilage offers a promising alternative. In was quantified using RT-qPCR for COL10 expression and development, mesenchymal stem cells become chondrocytes and visualized through histological analysis for Type X Collagen, transdifferentiate into bone through endochondral ossification. glycosaminoglycan, and alkaline phosphatase (ALP). Preliminary Through directed differentiation, induced pluripotent stem cellsresults indicate Indian Hedgehog Pathway activation increased (iPSCs) may develop into chondrocytes and then transdifferentiatehe number of hypertrophic chondrocytes but degraded tissue into bone, generating a tissue containing bone and cartilage. integrity, reducing glycosaminoglycans. Thyroid hormone We aim to optimize this process by determining factors enhanced hypertrophy by increasing hypertrophic chondrocytes required to transition chondrocytes into osteoblasts. We and increasing glycosaminoglycan production. Phosphate hypothesized that by enhancing hypertrophy, supplementing supplementation mineralized the tissue matrix after eight weeks with phosphate, and activating Wnt signalling, iPSC-derived of BMP-4 treatment, as indicated by ALP staining. RT- hypertrophic chondrocytes will develop a robust and mineralized qPCR and Wnt signaling results are forthcoming.This study Type X Collagen matrix, and hypertrophic chondrocytes provides preliminary insights into an iPSC-derived endochondral will transdifferentiate into osteoblasts. Human iPSCs were ossification model that may generate cartilage-bone tissue differentiated into hypertrophic chondrocytes via TGF-β treatmentonstructs for treating degenerative cartilage diseases. (2 weeks) followed by BMP-4 treatment (up to 12 weeks).
Source:
Harvard / Aryenne Ysabelle Rodrigo, Yumin Zhu, Elsie Sunderland, Zhiji Hu / 2025
Topics:
chondrocyte, cell, cartilage, perturbation, tissue, type, hypertrophic, model, gene, osteoblast, hypertrophy, ipsc
