# Navigating the landscape of direct cellular reprogramming with DiReG

## TL;DR

This paper introduces a web application to streamline the discovery of transcription factors for direct cellular reprogramming, improving efficiency and accessibility in regenerative medicine.

## Contribution

A unified web platform integrating computational tools and a RAG system for efficient TF discovery and validation in direct reprogramming.

## Key findings

- Current computational methods for reprogramming lack robust benchmarking standards.
- The introduced web application combines multiple tools and literature querying for TF prediction.
- The platform enhances accessibility and efficiency of transcription factor discovery for reprogramming.

## Abstract

Direct cellular reprogramming, converting one differentiated cell type directly into another, holds immense promise for regenerative medicine, developmental biology, and disease modeling. Identifying optimal transcription factor (TF) combinations to control this process remains complex and labor-intensive. Over the last decade, various computational tools emerged to infer TF sets for reprogramming. However, current methodologies possess critical limitations, and the absence of robust benchmarking standards makes it impossible to precisely validate and compare their performance. To address these challenges, we present a comprehensive analysis of existing computational methods for direct reprogramming and introduce a web application designed to support researchers in identifying and validating optimal TF sets. Our platform integrates predictions from established tools, incorporates a state-of-the-art Retrieval-Augmented Generation (RAG) system for efficient literature querying, and offers tools to further validate predictions. By providing a unified and interactive resource, our web application enhances the accessibility and efficiency of TF discovery for direct reprogramming. Furthermore, we discuss critical limitations shared by current methodologies and highlight the need for computational tools that can account for the complex regulatory dynamics of direct reprogramming. This work not only advances the toolkit available to researchers but also lays the groundwork for future innovations aimed at realizing the full potential of direct reprogramming.