Machine Learning Approaches for the Integrative Analysis of Multi-omics Data

Multi-omics data is a collective term which refers to multiple levels of “-omic” sequencing datasets. It can provide a comprehensive understanding of the regulatory mechanisms that link the genotype to phenotype. A large number of “omics” datasets have been generated from studies in various biological scenarios but there is a need for advanced analytical tools that derive meaningful biological insights from these datasets. In this thesis, three projects have been developed for integrating multiple “omics” datasets to answer distinct biological questions. In the first project, dimension reduction and clustering methods are applied on single cell RNA-sequencing data from lung endothelial cells to identify the cellular heterogeneity within the lung endothelium during lung injury and regeneration. We identified three major subpopulations in lung endothelial cells at baseline and at the time points post injury. One subpopulation is enriched for the expression of immune-related genes while another subpopulation is enriched for the expression of developmental genes. In the second project, a Bayesian Inference model, BITFAM, was developed to infer the transcription factors activities in single cells by integrating single cell RNA-seq data and bulk ChIP-seq data. We were able to validate that BITFAM could indeed infer the transcription factors activities using known biological functions as well as a publicly available dataset in which transcription factor deletion was achieved by CRISPR/Cas9 targeting of transcription factors. In the third project, we assessed the relative effect of DNA sequences and epigenetics modifications on gene expression using a deep learning framework, iSEGnet. I investigated the optimal regions that achieve the best prediction of gene expression. I also explored the most important regions and epigenetics modifications that impact gene expression as well as the regulatory mechanisms in these regions. These projects highlight the value of using machine learning and deep learning approaches to analyze multi-omic datasets and thereby identify regulatory mechanisms underlying gene expression

Rhodium-Catalyzed Hydroacylation of <i>para</i>-Quinone Methides with Salicylaldehydes: An Approach to α,α-Diaryl-2-Hydroxy Acetophenones

A rhodium-catalyzed hydroacylation of <i>para</i>-quinone methides (<i>p</i>-QMs) with salicylaldehydes has been disclosed. This method allows for the construction of α,α-diaryl-2-hydroxy acetophenones through tandem C–H activation/C–C bond formation/aromatization process. Moreover, this unprecedented hydroacylation of trisubstituted alkenes exhibits good yields with broad functional group tolerance as well as gram-scale capacity

Sequence Effect on the Topology of 3 + 1 Interlocked Bimolecular DNA G‑Quadruplexes

Electrospray ionization mass spectrometry (ESI-MS) combined with fluorescence, circular dichroism, UV spectrophotometer, and native polyacrylamide gel electrophoresis techniques are used to study structural features of interlocked dimers formed by DNA sequence 93del (GG­G­G­T­G­G­G­A­G­G­A­G­G­GT) and its derivatives. Herein, we demonstrate that the interlocked dimers can be distinguished from stacked dimers formed by sequences T30923 (GG­G­T­G­G­G­T­G­G­G­T­G­G­GT) and T30177 (GT­G­G­T­G­G­G­T­G­G­G­T­G­G­GT). In addition, loop length, the base at 5′-end, and the isolation of T and TT to the first 4G tract do significantly influence the formation and topologies of interlocked dimers. Furthermore, our results suggest that the 4G tract and the 2G tract in various locations in the 93del derivative sequence can form interlocked structure. This work not only provides new insight into the assembly of 3 + 1 interlocked DNA conformations but also demonstrates that ESI-MS combined with other analytical methods is rapid and useful for DNA structural studies

MalishEtAl2023_Ecosphere

Data: Files ending in _current of _future contain hydrological model output, used to caclulate continuity and connectivity metrics. File in map_stats folder contain continuity metric values. blue_fixed.rda and connectivity_wts.csv are used to calculate DCI. Code: ConnectivityMetrics.R contains code to calculate percent wet length, number of dry fragments, and average length of dry fragments. DCI.R contains code to calculate DCI. change_dryperiodlength.R, change_dryperiods.R, and change_zeroflowdays.R contain code to calculate change in continuity metrics.</p

Accessing 1,3-Dienes via Palladium-Catalyzed Allylic Alkylation of Pronucleophiles with Skipped Enynes

An unprecedented palladium-catalyzed allylic alkylation of pronucleophiles with unactivated skipped enynes has been developed. This method provides a straightforward access to a wide array of 1,3-dienes without the need to preinstall leaving groups or employ extra oxidants. The reaction exhibited high atom economy, good functional group tolerance, excellent regioselectivities, and scalability. With D₂O as cosolvent, deuterium could be incorporated in high efficiency

Controllable Rh(III)-Catalyzed Annulation between Salicylaldehydes and Diazo Compounds: Divergent Synthesis of Chromones and Benzofurans

A Rh­(III)-catalyzed annulation between salicylaldehydes and diazo compounds with controllable chemoselectivity is described. AgNTf₂ favored benzofurans via a tandem C–H activation/decarbonylation/annulation process, while AcOH led to chromones through a C–H activation/annulation pathway. The reaction exhibited good functional group tolerance and scalability. Moreover, only a single regioisomer of benzofuran was obtained due to the in situ decarbonylation orientation effect

Accessing 1,3-Dienes via Palladium-Catalyzed Allylic Alkylation of Pronucleophiles with Skipped Enynes

An unprecedented palladium-catalyzed allylic alkylation of pronucleophiles with unactivated skipped enynes has been developed. This method provides a straightforward access to a wide array of 1,3-dienes without the need to preinstall leaving groups or employ extra oxidants. The reaction exhibited high atom economy, good functional group tolerance, excellent regioselectivities, and scalability. With D₂O as cosolvent, deuterium could be incorporated in high efficiency

Accessing 1,3-Dienes via Palladium-Catalyzed Allylic Alkylation of Pronucleophiles with Skipped Enynes

An unprecedented palladium-catalyzed allylic alkylation of pronucleophiles with unactivated skipped enynes has been developed. This method provides a straightforward access to a wide array of 1,3-dienes without the need to preinstall leaving groups or employ extra oxidants. The reaction exhibited high atom economy, good functional group tolerance, excellent regioselectivities, and scalability. With D₂O as cosolvent, deuterium could be incorporated in high efficiency