Biology subjects

Dina Zielinski

Publications and source records attributed to Dina Zielinski.

4 recordsLinked to original sources

bioRxiv2016

Genome-wide profiling of heritable and de novo STR variations

Short tandem repeats (STRs) are highly variable elements that play a pivotal role in multiple genetic diseases, population genetics applications, and forensic casework. However, STRs have proven problematic to genotype from high-throughput sequencing data. Here, we describe HipSTR, a novel haplotype-based method for robustly genotyping, haplotyping, and phasing STRs from whole genome sequencing data and report a genome-wide analysis and validation of de novo STR mutations.

Genomics↗

bioRxiv2016

Capacity-approaching DNA storage

DNA is an attractive medium to store digital information. Here, we report a storage strategy, called DNA Fountain, that is highly robust and approaches the information capacity per nucleotide. Using our approach, we stored a full computer operating system, movie, and other files with a total of 2.14 x 106 bytes in DNA oligos and perfectly retrieved the information from a sequencing coverage equivalent of a single tile of Illumina sequencing. We also tested a process that can allow 2.18 x 1015 retrievals using the original DNA sample and were able to perfectly decode the data. Finally, we explored the limit of our architecture in terms of bytes per molecules and obtained a perfect retrieval from a density of 215Petabyte/gram of DNA, orders of magnitudes higher than previous techniques.

Synthetic Biology↗

bioRxiv2015

Biological screens from linear codes: theory and tools

Molecular biology increasingly relies on large screens where enormous numbers of specimens are systematically assayed in the search for a particular, rare outcome. These screens include the systematic testing of small molecules for potential drugs and testing the association between genetic variation and a phenotype of interest. While these screens are \"hypothesis-free,\" they can be wasteful; pooling the specimens and then testing the pools is more efficient. We articulate in precise mathematical ways the type of structures useful in combinatorial pooling designs so as to eliminate waste, to provide light weight, flexible, and modular designs. We show that Reed-Solomon codes, and more generally linear codes, satisfy all of these mathematical properties. We further demonstrate the power of this technique with Reed-Solomonbased biological experiments. We provide general purpose tools for experimentalists to construct and carry out practical pooling designs with rigorous guarantees for large screens.

Bioinformatics↗

bioRxiv2013

OTX2 Dosage Sensitivity is Implicated in Hemifacial Microsomia

Hemifacial microsomia (HFM) is the second most common facial anomaly after cleft lip and palate. The phenotype is highly variable and most cases are sporadic. Here, we investigated the disorder in a large pedigree with five affected individuals spanning eight meioses. We performed whole-exome sequencing and a genome-wide survey of segmental variations. Analysis of the exome sequencing results indicated the absence of a pathogenic coding point mutation. Inspection of segmental variations identified a 1.3Mb duplication of chromosome 14q22.3 in all affected individuals that was absent in more than 1000 chromosomes of ethnically matched controls. The duplication was absent in seven additional sporadic HFM cases, which is concordant with the known heterogeneity of the disorder. To find the critical gene in the duplicated region, we analyzed signatures of human craniofacial disease networks, mouse expression data, and predictions of dosage sensitivity. All of these approaches implicated OTX2 as the most likely causal gene. Moreover, OTX2 is a known oncogenic driver in medulloblastoma, a condition that was diagnosed in the proband during the course of our study. Our findings highlight dosage sensitivity of OTX2 in human craniofacial development and suggest a possible shared etiology between a subtype of hemifacial microsomia and medulloblastoma.

Genetics↗