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Protein Sciences

One Stop Shop for Research Protein Generation

With multiple platforms for protein generation, we produce diverse research grade proteins and antibodies to fit your needs.

Bioinformatics

Bioinformatics is a time-saving and cost-effective method to analyze a batch of molecules in a short amount of time, thereby, facilitating the protein engineering and host cell engineering process.

 

WuXi Biologics provides comprehensive bioinformatics solutions covering every stage of biologics development. Our tool suites include in silico mAbs assessment, antibody engineering, hybridoma sequencing, single B cell sequencing, host cell genome assembly and analysis, CRISPR gRNA design and gene editing, on-target and off-target analysis, CRISPR library screening, cell engineering, and NGS analysis. Each tool has a user-friendly interface, complete readme text, and normative report files. At every stage of your project, we provide detailed consultation and service.

 

In Silico mAb Assessment

We provide complete toolbox for in silico assessment of antibody developability, including aggregation prediction, immunogenicity prediction (humanness), PTM prediction, sequence liability evaluation, and solubility prediction.

 

  • Aggregation Prediction
  • Immunogenicity Prediction and Antibody Humanization
  • PTM Prediction
  • Sequence Liability Evaluation
  • Solubility Prediction

Case Study

No Aggregation

 

We can reduce the aggregation risk by protein structure features. Also, we may construct dedicated machine learning model by sequence features as well as structural features.

Aggregation

 

Antibody Engineering

We provide structure-based and sequence-based antibody engineering to reduce developability issues.

 

  • Sequence-based Antibody Engineering
  • Structure-based Antibody Engineering

Case Study

We could deliver 10 optimized candidate sequences with reduced developability issues for each antibody within 1 week. We also provide our detail proof about every change of antibody to help you optimize your antibody.

Hybridoma Sequencing

Getting ready-to-express antibody sequences with complete annotations from sorted hybridoma cells by Illumina sequencing.

 

Single-cell BCR-seq

Getting ready-to-express antibody sequences with VDJ annotations from enriched B cells (from animal or human peripheral blood) by 10x single B cell sequencing.

 

Case Study

Starting from 105 antigen-enriched mouse B cells, we finish the single-cell BCR library preparing and sequencing, and data analysis. 5499 paired BCR were obtained, and by sequence filtering and clustering, 187 IgG1 VH-VL were identified.

 

CRISPR Library Design

The diagram of WuXi CRISPR guide RNA design tool.

High specific gRNA library is designed based on the genome information, and the on-target and the off-target are monitored by our NGS analysis toolkits.

Case Study

WuXi Biologics have designed a whole genome CRISPR library using our own high-quality and well-annotated CHO-K1 genome. This allow us to perform whole genome CRISPR screens to identify genes related to protein expression and quality. Below shows a typical workflow.

CRISPR Off-Target Identification

The main obstacle of CRISPR application is off-target effect. To identify CRISPR off-target sites, we provide both in silico and experimental methods.

 

In silico predict the potential off-target sites on whole genome by both bioinformatics methods and deep learning models.

 

We could predict the off-target sites not only with mismatches between gRNA and genome, but also with bulge between gRNA and genome.

 

CRISPR-Net: A Recurrent Convolutional Network Quantifies CRISPR Off-Target Activities with Mismatches and Indels. Advanced Science, 2020.

Off-target Analysis with NGS Analysis

 

  • First mapping WGS data to host genome, and analysis the broken sites. Combining the information of guide RNA sequence, the off-target sites are identified.
  • The timeline from receiving cell sample to deliver the identified off-target sites could be finished within 2 weeks.

 

Integration Site identification

Methods Size of sequencing data Timeline
Illumina sequencing 100G 2 weeks
Nanopore sequencing 15~20G 1 week

 

Integration site identification could be used monoclonal validation and copy number analysis. WuXi Biologics provides two candidate methods for integration site identification:

Case Study

Integration sites analysis was implemented on a cell line expressing mAbs. Nanopore sequencing generated ~20G data. Total of 10 integration sites were identified.

Sequence No. of integration site identification
HC 10
LC 9

De Novo Genome Assembly

Having genome information is essential for many downstream genetic applications. We provide a de novo genome assembly package to get high-quality genome sequence with full annotation. The final delivery results including genome sequence, coding gene sequence, protein sequence, GO/KEGG annotation information, etc.

 

The contents of de novo genome assembly services

Having genome information helps many downstream applications, such as:

 

(1) NGS analysis, including SNP, copy number variation, structure variation, expression level, DNA methylation, ATAC etc.;

 

(2) Designing CRISPR gRNA for gene editing and/or library screening, designing ZFN/ZFP for gene editing, and analyzing the on- and off-target of editing results;

 

(3) Identifying integration sites for the cell line characterizations.

 

Introduction to de novo genome assembly

Case Study

Figure 3. The results of de novo genome assembly of a CHO-K1 host cell.

WuXi Bio CHO-K1 host cell was sequenced and assembled. The contig N50 is 48 times higher than the NCBI genome, which remarkably increases the accuracy of WGS and RNA-seq analysis.

Mutation Detection

 

The stability of host cell genome and completeness of key genes and pathways are fundamental for stable cell line development. WuXi Biologics provides mutation analysis for risk evaluation of cell line genome. The time line from receiving cell samples to deliver mutation analysis will be finished within 2 weeks.

 

Mutation detection offers:

 

  • WGS Sequencing
  • Mutation Detection
  • Mutation Annotation
  • Risk of Mutation Prediction

Case Study

For plasmid sequence validation, WuXi Biologics offers mutation detection with in-house developed algorithm. The detection limitation reaches to 0.2%.