Shaojie Zhang

Abstract

The University of Central Florida and the University of Texas Health Science Center have developed technologies for genetic genealogical discovery in genotype databases:

• Invention 11227: Random Projection for IBD Detection (RaPID) software provides a fast, efficient method for detecting Identical-by-Descent (IBD) segments in a panel with phased haplotypes. While genetic relatedness, usually manifested as segments IBD, is ubiquitous in modern large biobanks, current IBD detection methods are not efficient at such a scale. RaPID achieves a time and space complexity linear to the input size and the number of reported IBDs. With simulation, the researchers showed that RaPID is orders of magnitude faster than existing methods while offering competitive power and accuracy. In UK Biobank, RaPID identified 3,335,807 >10cM IBDs among 223,507 male X-chromosomes in 11 minutes on a single core. RaPID is adaptable to data from different genotyping platforms with varying marker density and error rates.
  
  
• Invention 11570: The invention is a computer-based system and method for indexing, updating, and searching haplotypes for genetic genealogical discovery in genotype databases. It includes a pool of Positional Burrows-Wheeler transform (PBWT) genetic indexes, a haplotype ingestion engine, and a haplotype query engine. The haplotypes of individuals in a genotype database are indexed by a pool of multiple panels, each a PBWT data structure over a subset of markers of the original genotyping panel. Each panel pool can be updated by dynamic-PBWT insertion and deletion algorithms. The system identifies ancestral relationships by finding all long Identical-by-Descent (IBD) segments between a query and a panel, independent of the number of haplotypes.
  
  A genetic genealogical query of a haplotype against a database starts by projecting the query onto a subset of panels in the pool, then conducting PBWT long match queries over each panel. The system then aggregates the identified long matches into IBD segments (DNA matches) between the query and the haplotypes in the database. System implementation includes storing the projected panels in persisted random-access media (for example, RAM or SSD).

Partnering Opportunity

The research team is looking for partners to develop the technology further for commercialization.

Stage of Development

Prototype available.

Benefit

Market Application

Publications

Efficient haplotype matching between a query and a panel for genealogical search, Bioinformatics, Volume 35, Issue 14, July 2019, Pages i233–i241

RaPID: ultra-fast, powerful, and accurate detection of segments identical by descent (IBD) in biobank-scale cohorts. Genome Biology 20, 143 (2019)

Abstract

Researchers at the University of Central Florida and the University of Massachusetts have developed a CRISPR-based system for detecting DNA repeat expansion sequences—genetic mutations that cause diseases such as amyotrophic lateral sclerosis (ALS). The CRISPR Arrayed Repeat Detection System (CARDS) can detect multiple mutated genes simultaneously in a single assay. Additionally, the system’s unique CRISPRainbow technology enables scientists to simultaneously label as many as six target loci in live cells with a distinctive color. Overall, the system provides a means to resolve the 3D genome in live cells and track chromosome dynamics in real-time.

Technical Details

Based on the CRISPR technology, CARDS locates, labels and tracks the movements of DNA without editing/cutting the genome. CARDS tags specific locations along the genome by using its unique CRISPRainbow technology, a novel combination of a nuclease-dead Cas9 (dCas9) protein and an engineered single-guide RNA (sgRNA) sequence. A mutation in the dCas9 protein makes the nuclease inactive so that it only binds to the DNA but does not cleave it. The scaffolds of the sgRNA bind sets of fluorescent proteins that can be further combined to generate additional colors. For example, the technology can be used to simultaneously label six distinct chromosomal loci with different colors (such as red, green, blue, yellow, cyan and magenta) and observed in real-time with fluorescence microscopy.

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Market Application

Publications

Multiplexed labeling of genomic loci with dCas9 and engineered sgRNAs using CRISPRainbow, Nature Biotechnology, vol. 34,5 (2016): 528-30. DOI:10.1038/nbt.3526,

Abstract

Researchers at the University of Central Florida have developed four inventions to enhance netlist analysis. A netlist is a description of the connectivity of an electronic circuit. Together, the tools can help to detect code flaws and malicious logic in integrated circuits (ICs) and assure IC integrity and accessibility. They can also enable exports of netlists for use by other analysis tools and provide graphical views of a netlist. Following are brief descriptions of the inventions:

• RERTL, the UCF Register Transfer Level (RTL) code recovery tool: RTL code is specialized computer language used to describe the structure and behavior of electronic circuits. UCF’s RERTL leverages advanced graph algorithms to assist in netlist analysis. Typically, design defects (due to the influence of complex third-party IP designs with shorter time-to-market constraints or even malicious code) may be found and corrected with knowledge of RTL. Yet, these flaws may not be detected if third-party IP designs do not use or allow access to the RTL source code. Supported by RERTL, these logical states and their interactions are recovered and converted into human-readable RTL.


• Netlist Assessment Toolset (NETA): A software toolset, NETA aids IP users in assuring the confidentiality, integrity, and accessibility of their Integrated Circuit (IC) or third-party IP core. Ensuring the quality and trustworthiness of third-party resources has been a hard problem to tackle. Researchers have shown that analyzing ICs without golden models is challenging. The discussed toolset gives access to a slew of gate-level analysis tools, many of which are heuristic-based for extracting high-level circuit design information.


• NetA Verilog Exporter for Yosys: The UCF plugin is for the open-source Yosys netlist synthesis tool that exports netlists in a form usable by NETA, a suite of netlist analysis tools created by UCF and the University of Florida.


• NetViz: A graphical interface (GUI) for hardware security work, NetViz allows users to run multiple existing tools (the NETA toolset) with a graphical view of the netlist and the tool results. It also chains the tools together in a helpful way.

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Market Application