Challenge by Retro Biosciences

LONGEVITY GENE/PROTEIN KB

Extract knowledge from all publicly available sources regarding protein sequence-to-function relationships to empower future protein and gene reengineering efforts against aging.

> THE_PROBLEM

Given a human protein X — how do we extract knowledge from all publicly available sources regarding its sequence-to-function relationship to empower future protein and gene reengineering efforts?

Protein reengineering efforts are often bottlenecked by lack of sufficient sequence-to-function data that would inform first rounds of designs. This challenge aims to create a comprehensive knowledge base of known protein modifications linked to functional outcomes in experiments.

> OVERVIEW

MISSION AND GOALS

The mission is to speed up research on protein engineering, especially in the context of aging. The aggregated data will help researchers identify the most promising approaches to modifying wild-type protein sequences.

Essentially, an agent is expected to reproduce a GenAge type database but writing actual articles about the protein/gene sequence-to-function relationships related to longevity.

> REQUIREMENTS

1. USE WIKICROW AS REFERENCE

For starters, you can use WikiCrow by FutureHouse as a reference format (Wikipedia-style articles about genes, e.g. APOE).

2. MAPPING PROTEIN/GENE SEQUENCE TO FUNCTION

This is the key requirement! The system must establish clear relationships between protein/gene sequences and their functional outcomes related to longevity.

3. COMPREHENSIVE ARTICLES

Write articles about protein/gene sequence-to-function relationships related to longevity. Include information about:

• Evolutionary conservation
• Orthologs/paralogs across species
• Known genetic interventions
• Mutant strains data

😍 BONUS FEATURES

Small molecule binding data — integrate binding information for additional context

Tunable coarse-graining — from individual nucleotides/amino acids to larger domains or even families of domains

> EVALUATION

Breadth of Coverage

25%

Can your approach be applied to any human gene?

Depth of Evidence

25%

Can your approach recover at least 5 various sources of modifications for each gene?

Relation to Aging

30%

Is your source of protein sequence modification data relevant to aging? Is there association with lifespan?

Source Citations

20%

Bonus points if agent extracts original figures with key data from source studies and cites them in the article.

> OUTPUT

DATA STRUCTURE

Gene/Protein Name/ID <> 
Protein/DNA Sequence <> 
Interval in Sequence <> 
Function (text format)

PROTEIN IDENTIFIER

Use standard protein name and/or Uniprot ID linked to a protein sequence

ANNOTATIONS TABLE

Specify intervals in the protein sequence & introduced modifications and the change in function the modifications induced

> TEST_CASES

Test your agent with these specific proteins to validate its capability to extract comprehensive sequence-to-function relationships:

TEST CASE 1: NRF2

Your agent should be able to find:

  • Neoaves have a KEAP1 mutation that leads to over-active NRF2 (PMC7234996)
  • SKN-1 (nematode's ortholog of NRF2) increases lifespan in C.elegans (PMID: 28612944)

TEST CASE 2: SOX2

Should be able to recover the results of SuperSOX:

  • SuperSOX study — Modified SOX2 with enhanced reprogramming capabilities

TEST CASE 3: APOE

Should recover all major APOE variants and their longevity associations:

  • APOE2 — protective variant associated with longevity
  • APOE3 — common neutral variant
  • APOE4 — risk variant for Alzheimer's and reduced longevity

TEST CASE 4: OCT4

Should recover papers converting OCT6 into a reprogramming factor:

  • EMBR study — Converting OCT6 into reprogramming factor through sequence modifications

> SPECIFICATIONS

KNOWLEDGE BASE STRUCTURE

Gene/Protein Name/ID
    ↓
Protein/DNA Sequence
    ↓
Interval in Sequence
    ↓
Function (Text Format)
    ↓
Modification Effects
    ↓
Longevity Association

The desired structure should enable researchers to quickly identify sequence intervals of interest, understand their functional roles, and see how modifications in those regions affect longevity-related outcomes.

> RESOURCES

USEFUL DATABASES & TOOLS

LITERATURE & ARCHIVES

PROTEIN DATABASES

LONGEVITY DATABASES

  • GenAge

    Database of aging-related genes

  • Open Genes

    Longevity-associated genes database

FUNCTIONAL ELEMENTS

  • ELM

    Eukaryotic Linear Motif resource

> IMPACT

Having a clear knowledge base of known protein modifications linked to functional outcomes in experiments is going to speed up research on protein engineering, especially in the context of aging.

IMMEDIATE BENEFITS

  • • Faster protein engineering iterations
  • • Informed design decisions from day one
  • • Reduced experimental failures
  • • Better starting points for modifications

LONG-TERM IMPACT

  • • Accelerated anti-aging interventions
  • • Cross-species insights integration
  • • Democratized access to expertise
  • • Foundation for AI-driven design

Ready to accelerate protein engineering for longevity? Build the knowledge base that will transform aging research.