Error Correction for DNA Sequencing via Disk Based Index and Box Queries

The vast increase in DNA sequencing capacity over the last decade has quickly turned biology into a data-intensive science. Nevertheless, current sequencers such as Illumia HiSeq have high random per-base error rates, which makes sequencing error correction an indispensable require-ment for many sequence analysis applications. Most existing methods for error correction demand large expensive memory space, which limits their scalability for handling large datasets. In this thesis, we introduce a new disk based method, called DiskBQcor, for sequencing error correction. DiskBQcor stores k-mers for sequencing genome data along with their associated metadata in a disk based index tree, called the BoND-tree, and uses the index to efficiently process specially designed box queries to obtain relevant k-mers and their occurring frequencies. It takes an input read and locates the potential errors in the sequence. It then applies a comprehensive voting mech-anism and possibly an efficient binary encoding based assembly technique to verify and correct an erroneous base in a genome sequence under various conditions. To overcome the drawback of an offline approach such as DiskBQcor for wasting computing resources while DNA sequecing is in process, we suggest an online approach to correcting sequencing errors. The online processing strategies and accuracy measures are discussed. An algorithm for deleting indexed k-mers from the BoND-tree, which is a step stone for the online sequencing error correction, is also introduced. Our experiments demonstrate that the proposed methods are quite promising in error correction for sequencing genome data on disk. The resulting BoND-tree with correct k-mers can also be used for sequence analysis applications such as variant detection.Master of ScienceComputer and Information Science, College of Engineering and Computer ScienceUniversity of Michigan-Dearbornhttps://deepblue.lib.umich.edu/bitstream/2027.42/136615/3/Thesis_YarongGu_519_corrected.pd

The Landscape of Accessible Chromatin during Yak Adipocyte Differentiation

Although significant advancement has been made in the study of adipogenesis, knowledge about how chromatin accessibility regulates yak adipogenesis is lacking. We here described genome-wide dynamic chromatin accessibility in preadipocytes and adipocytes by using the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), and thus revealed the unique characteristics of open chromatin during yak adipocyte differentiation. The chromatin accessibility of preadipocytes and adipocytes exhibited a similar genomic distribution, displaying a preferential location within the intergenic region, intron, and promoter. The pathway enrichment analysis identified that genes with differential chromatin accessibility were involved in adipogenic metabolism regulation pathways, such as the peroxisome proliferator activated receptor-γ (PPAR) signaling pathway, wingless-type MMTV integration site (Wnt) signaling pathway, and extracellular matrix-receptor (ECM–receptor) interaction. Integration of ATAC-seq and mRNA-seq revealed that genes with a high expression were associated with high levels of chromatin accessibility, especially within 1 kb upstream and downstream of the transcription start site. In addition, we identified a series of transcription factors (TFs) related to adipogenesis and created the TF regulatory network, providing the possible interactions between TFs during yak adipogenesis. This study is crucial for advancing the understanding of transcriptional regulatory mechanisms of adipogenesis and provides valuable information for understanding the adaptation of plateau species to high-altitude environments by maintaining whole body homeostasis through fat metabolism

Synthesis and Study of CdSe QDs by a Microfluidic Method and via a Bulk Reaction

In this work, we synthesized monodispersed CdSe quantum dots (QDs) by a microfluidic method and via a bulk reaction. The structures of the CdSe QDs were characterized by X-ray powder diffraction (XRD) and high-resolution transmission electron microscopy (HR-TEM). The optical properties of the prepared CdSe QDs were determined using ultraviolet-visible absorption spectroscopy and photoluminescence spectroscopy. The CdSe QDs obtained by the microfluidic method have a faster crystal growth rate and a higher absolute photoluminescence quantum yield than those obtained via the bulk reaction. Additionally, we investigated the growth process of the CdSe QDs with increasing residence times.ISSN:2073-435

Pressure-Induced Emission Enhancement of Carbazole: The Restriction of Intramolecular Vibration

Pressure-induced emission enhancement (PIEE), a novel phenomenon in the enhancement of the solid-state emission efficiency of fluorophores, has been arousing wide attention in recent years. However, research on PIEE is still in the early stage. To further pursue more enhanced efficiency, discovering and designing more PIEE systems would be urgently desirable and of great importance. In this Letter, we found that carbazole presented a conspicuous emission enhancement under high pressure up to 1.0 GPa. In situ high-pressure infrared spectroscopy and angle-dispersive X-ray diffraction analysis combined with Hirshfeld surface theory calculation indicated that the PIEE of carbazole was attributed to the decrease of the nonradiation vibration process. This phenomenon mainly resulted from restriction of the N–H stretching vibration by increased N–H···π interactions under high pressure. Our study puts forward a mechanism of PIEE related to the restriction of intramolecular vibration, which provided deep insight into the essential role of intermolecular interaction in fluorescence emission properties

Clickable Protein Nanocapsules for Targeted Delivery of Recombinant p53 Protein

Encapsulating anticancer protein therapeutics in nanocarriers is an attractive option to minimize active drug destruction, increase local accumulation at the disease site, and decrease side effects to other tissues. Tumor-specific ligands can further facilitate targeting the nanocarriers to tumor cells and reduce nonspecific cellular internalization. Rationally designed non-covalent protein nanocapsules incorporating copper-free “click chemistry” moieties, polyethylene glycol (PEG) units, redox-sensitive cross-linker, and tumor-specific targeting ligands were synthesized to selectively deliver intracellular protein therapeutics into tumor cells via receptor-mediated endocytosis. These nanocapsules can be conjugated to different targeting ligands of choice, such as anti-Her2 antibody single-chain variable fragment (scFv) and luteinizing hormone releasing hormone (LHRH) peptide, resulting in specific and efficient accumulation within tumor cells overexpressing corresponding receptors. LHRH-conjugated nanocapsules selectively delivered recombinant human tumor suppressor protein p53 and its tumor-selective supervariant into targeted tumor cells, which led to reactivation of p53-mediated apoptosis. Our results validate a general approach for targeted protein delivery into tumor cells using cellular-responsive nanocarriers, opening up new opportunities for the development of intracellular protein-based anticancer treatment