Our broad research interest is to improve the molecular diagnosis and clinical care of patients with Mendelian disorders. On the translational side, we aim to bring transformative technologies and concepts to clinical diagnostics. On the discovery side, we strive to empower diagnostic resources and clinical big data to stimulate research investigations. Below are several ongoing projects.

Diagnostic RNA-seq and cell trans-differentiation

A fundamental obstacle in the clinical application of diagnostic RNA-seq is that the genes of interest are not always adequately expressed in the clinically accessible tissues. We are developing protocols to activate the genes of interest by trans-differentiating available patient cells to the desired cell type. The goal is to optimize the protocols so that they are low cost, rapid, and can be applied at scale in a clinical workflow. We have successfully converted human fibroblasts into induced neurons to help the interpretation of variants associated with neurological disorders. This workflow is being applied to patients from the Undiagnosed Diseases Network (UDN) project to improve the molecular diagnostic yield.

Implementing a low-cost sequencing technology into clinical diagnostics

We are collaborating with a new biotechnology company, Ultima Genomics, to bring low-cost next generation sequencing to clinical diagnostics. The Ultima sequencer can deliver whole genome sequencing for a human specimen at a cost considerably lower than traditional methods. We are in the process of implementing and optimizing the wet lab set up, bioinformatics pipeline, and clinical interpretation processes for clinical diagnostics using whole genome sequencing and RNA-seq.

Characterization of clinically actionable genetic modifiers by sequencing individuals with large genomic deletions

We seek to sequence a group of individuals with large recurrent heterozygous genomic deletions to elucidate the impact and mechanisms of genetic modifiers. These selected individuals present two unique features, which allow us to detect from their genomic analysis disease-risk modifying alleles, especially those that are clinically meaningful, at an enhanced power compared to conventional GWAS studies. First, these unrelated individuals share identical large heterozygous deletions; second, they present a wide range of incompletely penetrant clinical phenotypes. We are currently studying two disorders as proof-of-concepts, the 17q12 deletions associated with diabetes and kidney cysts, and the distal 1q21 deletions associated with neurodevelopmental disorders. Findings from this project are expected to bridge the gap between our understanding of highly penetrant, rare Mendelian variants and variants with higher population frequencies and association with complex diseases.

Screening of genetic elements using segmental haploid human cell lines

We are establishing human cell lines derived from individuals with constitutional large heterozygous genomic deletions as models. These models can be used to conduct genetic screens, for example, CRISPR screens. Screening results from these ‘segmental haploid’ cell lines are expected to be more sensitive and more likely to be clinically meaningful than screening results obtained from traditional diploid or cancerous cell lines.

Pengfei Liu Ph.D.

Email:

pengfeil@bcm.edu

By Phone:

(713)-798-7725

Molecular and Human Genetics

Baylor College of Medicine

ACGME/ABMGG Laboratory Genetics and Genomics Fellowship Program

Baylor College of Medicine

Houston, Texas United States

NGS/Molecular

Baylor Genetics

One Baylor Plaza

Room 223E

Mail Stop BCM 225

Houston, TX 77030

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