The L1000 technology, a cost-effective high-throughput transcriptomics technology, has been appli... more The L1000 technology, a cost-effective high-throughput transcriptomics technology, has been applied to profile a collection of human cell lines for their gene expression response to > 30,000 chemical and genetic perturbations. In total, there are currently over 3 million available L1000 profiles. Such a dataset is invaluable for the discovery of drug and target candidates and for inferring mechanisms of action for small molecules. The L1000 assay only measures the mRNA expression of 978 landmark genes while 11,350 additional genes are computationally reliably inferred. The lack of full genome coverage limits knowledge discovery for half of the human protein coding genes, and the potential for integration with other transcriptomics profiling data. Here we present a Deep Learning two-step model that transforms L1000 profiles to RNA-seq-like profiles. The input to the model are the measured 978 landmark genes while the output is a vector of 23,614 RNA-seq-like gene expression profil...
Birth defects are functional and structural abnormalities that impact 1 in 33 births in the Unite... more Birth defects are functional and structural abnormalities that impact 1 in 33 births in the United States. Birth defects have been attributed to genetic as well as other factors, but for most birth defects there are no known causes. Small molecule drugs, cosmetics, foods, and environmental pollutants may cause birth defects when the mother is exposed to them during pregnancy. These molecules may interfere with the process of normal fetal development. To characterize associations between small molecule compounds and their potential to induce specific birth abnormalities, we gathered knowledge from multiple sources to construct a reproductive toxicity Knowledge Graph (ReproTox-KG) with an initial focus on associations between birth defects, drugs, and genes. Specifically, to construct ReproTox-KG we gathered data from drug/birth-defect associations from co-mentions in published abstracts, gene/birth-defect associations from genetic studies, drug- and preclinical-compound-induced gene ...
Motivation Many biological and biomedical researchers commonly search for information about genes... more Motivation Many biological and biomedical researchers commonly search for information about genes and drugs to gather knowledge from these resources. For the most part, such information is served as landing pages in disparate data repositories and web portals. Results The Gene and Drug Landing Page Aggregator (GDLPA) provides users with access to 50 gene-centric and 19 drug-centric repositories, enabling them to retrieve landing pages corresponding to their gene and drug queries. Bringing these resources together into one dashboard that directs users to the landing pages across many resources can help centralize gene- and drug-centric knowledge, as well as raise awareness of available resources that may be missed when using standard search engines. To demonstrate the utility of GDLPA, case studies for the gene klotho and the drug remdesivir were developed. The first case study highlights the potential role of klotho as a drug target for aging and kidney disease, while the second stu...
While cellular technology has become ubiquitous and effective in bridging the digital divide, bil... more While cellular technology has become ubiquitous and effective in bridging the digital divide, billions of households around the world remain unconnected and unserved. Increasing income and effective participation in governance are the gold standard in establishing the positive social impact of innovations that seek to provide access to communication in last mile areas, which are usually geographically isolated rural villages. Results from the social impact analysis of the Village Base Station Project (VBTS), using culturally-sensitive oral history, reveal that end-users use emotional terms, such as ginhawa and perhuwisyo in assessing how access to cellular networks affected their everyday life and social relationships. This article contributes to the scholarly discussions on the social impact of cellular technology by understanding end-users’ emotional responses as indicators of social impact. We argue that a more human-centered framework for social impact assessment requires a care...
A common stigma that students often associate with an engineering degree is enduring an excessive... more A common stigma that students often associate with an engineering degree is enduring an excessive workload. In fact, recent studies suggest that this perception is one of the primary reasons many students leave engineering majors and pursue other studies. This claim is also confirmed almost uniformly across all core engineering courses when students report on end of course surveys that they do not have enough time in their schedule to complete their assignments. As an educator, however, these claims are viewed from an admittedly critical perspective, especially after witnessing first-hand, frustratingly at times, poor study habits, weak time management skills and unacceptable daily preparation levels for class. In fact, this contradiction is highlighted further by a unique departmental policy requiring students to anonymously report how much time they spend preparing for each lesson. Each year, students report that they are actually spending on average just half the amount of time p...
Studies in health technology and informatics, 2020
Advancements in regenerative medicine have brought to the fore the need for increased standardiza... more Advancements in regenerative medicine have brought to the fore the need for increased standardization and sharing of stem cell product characterization to help drive these innovative interventions toward public availability. Although numerous attempts have been made to store this data, there is still a lack of a platform that incorporates heterogeneous stem cell information into a harmonized project-based framework. The aim of this project was to introduce and pilot-test an intelligent informatics solution which integrates diverse stem cell product characteristics with study subject and omics information. In the resulting platform, heterogeneous data is validated using predefined ontologies and stored in a NoSQL repository. Pilot-testing was performed on nine sponsored stem cell projects conducting preclinical and intervention evaluations. The pilot-testing demonstrated the robustness of the proposed platform, by seamlessly harmonizing diverse common data elements, and the potential...
The National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) initiati... more The National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) initiative has generated extensive phosphoproteomics and proteomics data for tumor and tumor-adjacent normal tissue across multiple cancer types. This dataset provides an unprecedented opportunity to systematically characterize pan-cancer kinase activities, which is essential for coupling tumor subtypes with kinase inhibitors as potential treatment. In this work, we performed Kinase Enrichment Analysis (KEA) using a CPTAC phosphoproteomics dataset to identify putative differences in kinase state between tumor and normal tissues within and across five types of cancer. We then implemented an interactive web-portal, the ProTrack Kinase Activity Portal (ProKAP), for querying, visualizing, and downloading the derived pan-cancer kinase activity scores together with the corresponding sample metadata, and protein and phosphoprotein expression profiles. To illustrate the usage of this digital resource, w...
Phosphoproteomics and proteomics experiments capture a global snapshot of the cellular signaling ... more Phosphoproteomics and proteomics experiments capture a global snapshot of the cellular signaling network, but these methods do not directly measure kinase state. Kinase Enrichment Analysis 3 (KEA3) is a webserver application that infers overrepresentation of upstream kinases whose putative substrates are in a user-inputted list of proteins. KEA3 can be applied to analyze data from phosphoproteomics and proteomics studies to predict the upstream kinases responsible for observed differential phosphorylations. The KEA3 background database contains measured and predicted kinase-substrate interactions (KSI), kinase-protein interactions (KPI), and interactions supported by co-expression and co-occurrence data. To benchmark the performance of KEA3, we examined whether KEA3 can predict the perturbed kinase from single-kinase perturbation followed by gene expression experiments, and phosphoproteomics data collected from kinase-targeting small molecules. We show that integrating KSIs and KPIs...
Imbalance in the finely orchestrated system of chromatin-modifying enzymes is a hallmark of many ... more Imbalance in the finely orchestrated system of chromatin-modifying enzymes is a hallmark of many pathologies such as cancers, since causing the affection of the epigenome and transcriptional reprogramming. Here, we demonstrate that a loss-of-function mutation (LOF) of the major histone lysine methyltransferase SETDB1 possessing oncogenic activity in lung cancer cells leads to broad changes in the overall architecture and mechanical properties of the nucleus through genome-wide redistribution of heterochromatin, which perturbs chromatin spatial compartmentalization. Together with the enforced activation of the epithelial expression program, cytoskeleton remodeling, reduced proliferation rate and restricted cellular migration, this leads to the reversed oncogenic potential of lung adenocarcinoma cells. These results emphasize an essential role of chromatin architecture in the determination of oncogenic programs and illustrate a relationship between gene expression, epigenome, 3D genom...
Although widely prevalent, Lyme disease is still under-diagnosed and misunderstood. Here we follo... more Although widely prevalent, Lyme disease is still under-diagnosed and misunderstood. Here we followed 73 acute Lyme disease patients and uninfected controls over a period of a year. At each visit, RNA-sequencing was applied to profile patients' peripheral blood mononuclear cells in addition to extensive clinical phenotyping. Based on the projection of the RNA-seq data into lower dimensions, we observe that the cases are separated from controls, and almost all cases never return to cluster with the controls over time. Enrichment analysis of the differentially expressed genes between clusters identifies up-regulation of immune response genes. This observation is also supported by deconvolution analysis to identify the changes in cell type composition due to Lyme disease infection. Importantly, we developed several machine learning classifiers that attempt to perform various Lyme disease classifications. We show that Lyme patients can be distinguished from the controls as well as fr...
To get an improved image or to obtain any useful information from it, image processing is a metho... more To get an improved image or to obtain any useful information from it, image processing is a method of implementing any operations on an image. In the method of classifying and detection of images, this process mainly contributes to the innovation of technology. The implementation of image processing in robots had been used in earlier but with different uses. Using FPV Camera 720p OIN in the projects lets it transmits live video streaming to any device attached to it. This paper shows the robustness of image processing as it detects defects on pipes. Covering the inner external part of the pipe, the robot can pass through inside the pipe. With the accuracy of 67%, the project will be tested in different pipes and drainages for the application.
Proceedings of the ACM on Human-Computer Interaction, 2019
This paper analyzes the processes and challenges of technology repair in remote, low-income areas... more This paper analyzes the processes and challenges of technology repair in remote, low-income areas far from standard ICT repair infrastructure. Our sites of study are the fishing and farming villages of Dibut, Diotorin, and Dikapinisan in Aurora Province, Philippines, located in coastal coves against a mountain range. Residents are geographically isolated from urban areas, with the nearest peri-urban center of Baler a boat trip of several hours away, infeasible in some sea conditions. Unlike prior work in more connected rural areas, there are no local repair shops and device repair is uncommon, despite frequent breakage due to harsh conditions for electronics. The scarcity of local electronics repair limits technology access and leads to accumulation of e-waste. While prior work demonstrates that local electronics repair capability does arise in many rural areas around the world, we must also acknowledge that the successful emergence of this infrastructure depends on the intersection...
The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH Common Fund program... more The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH Common Fund program with the goal of generating a large-scale and comprehensive catalogue of perturbation-response signatures by utilizing a diverse collection of perturbations across many model systems and assay types. The LINCS Data Portal (LDP) has been the primary access point for the compendium of LINCS data and has been widely utilized. Here, we report the first major update of LDP (http://lincsportal.ccs.miami.edu/signatures) with substantial changes in the data architecture and APIs, a completely redesigned user interface, and enhanced curated metadata annotations to support more advanced, intuitive and deeper querying, exploration and analysis capabilities. The cornerstone of this update has been the decision to reprocess all high-level LINCS datasets and make them accessible at the data point level enabling users to directly access and download any subset of signatures across the entire library i...
The Motif Finding Problem is a NP-complete problem which seeks to find small conserved sites in D... more The Motif Finding Problem is a NP-complete problem which seeks to find small conserved sites in DNA sequences. Though many algorithms have been created for this problem, most typically fail on subtle motifs like Pevzner and Sze's (15,4) motif challenge. PROJECTION algorithm improves the performance of existing motif finders by using random pro-jections to provide initial estimates for the motif finder. Pre-vious efforts to parallelize PROJECTION have been done to speed up the algorithm though these efforts either use O(x 2) work complexity by using multiple comparison or employ the CPU for hashing to find initial estimates. In this paper, we present an algorithm that uses parallel hashing to improve PROJECTION's computational time.
The L1000 technology, a cost-effective high-throughput transcriptomics technology, has been appli... more The L1000 technology, a cost-effective high-throughput transcriptomics technology, has been applied to profile a collection of human cell lines for their gene expression response to > 30,000 chemical and genetic perturbations. In total, there are currently over 3 million available L1000 profiles. Such a dataset is invaluable for the discovery of drug and target candidates and for inferring mechanisms of action for small molecules. The L1000 assay only measures the mRNA expression of 978 landmark genes while 11,350 additional genes are computationally reliably inferred. The lack of full genome coverage limits knowledge discovery for half of the human protein coding genes, and the potential for integration with other transcriptomics profiling data. Here we present a Deep Learning two-step model that transforms L1000 profiles to RNA-seq-like profiles. The input to the model are the measured 978 landmark genes while the output is a vector of 23,614 RNA-seq-like gene expression profil...
Birth defects are functional and structural abnormalities that impact 1 in 33 births in the Unite... more Birth defects are functional and structural abnormalities that impact 1 in 33 births in the United States. Birth defects have been attributed to genetic as well as other factors, but for most birth defects there are no known causes. Small molecule drugs, cosmetics, foods, and environmental pollutants may cause birth defects when the mother is exposed to them during pregnancy. These molecules may interfere with the process of normal fetal development. To characterize associations between small molecule compounds and their potential to induce specific birth abnormalities, we gathered knowledge from multiple sources to construct a reproductive toxicity Knowledge Graph (ReproTox-KG) with an initial focus on associations between birth defects, drugs, and genes. Specifically, to construct ReproTox-KG we gathered data from drug/birth-defect associations from co-mentions in published abstracts, gene/birth-defect associations from genetic studies, drug- and preclinical-compound-induced gene ...
Motivation Many biological and biomedical researchers commonly search for information about genes... more Motivation Many biological and biomedical researchers commonly search for information about genes and drugs to gather knowledge from these resources. For the most part, such information is served as landing pages in disparate data repositories and web portals. Results The Gene and Drug Landing Page Aggregator (GDLPA) provides users with access to 50 gene-centric and 19 drug-centric repositories, enabling them to retrieve landing pages corresponding to their gene and drug queries. Bringing these resources together into one dashboard that directs users to the landing pages across many resources can help centralize gene- and drug-centric knowledge, as well as raise awareness of available resources that may be missed when using standard search engines. To demonstrate the utility of GDLPA, case studies for the gene klotho and the drug remdesivir were developed. The first case study highlights the potential role of klotho as a drug target for aging and kidney disease, while the second stu...
While cellular technology has become ubiquitous and effective in bridging the digital divide, bil... more While cellular technology has become ubiquitous and effective in bridging the digital divide, billions of households around the world remain unconnected and unserved. Increasing income and effective participation in governance are the gold standard in establishing the positive social impact of innovations that seek to provide access to communication in last mile areas, which are usually geographically isolated rural villages. Results from the social impact analysis of the Village Base Station Project (VBTS), using culturally-sensitive oral history, reveal that end-users use emotional terms, such as ginhawa and perhuwisyo in assessing how access to cellular networks affected their everyday life and social relationships. This article contributes to the scholarly discussions on the social impact of cellular technology by understanding end-users’ emotional responses as indicators of social impact. We argue that a more human-centered framework for social impact assessment requires a care...
A common stigma that students often associate with an engineering degree is enduring an excessive... more A common stigma that students often associate with an engineering degree is enduring an excessive workload. In fact, recent studies suggest that this perception is one of the primary reasons many students leave engineering majors and pursue other studies. This claim is also confirmed almost uniformly across all core engineering courses when students report on end of course surveys that they do not have enough time in their schedule to complete their assignments. As an educator, however, these claims are viewed from an admittedly critical perspective, especially after witnessing first-hand, frustratingly at times, poor study habits, weak time management skills and unacceptable daily preparation levels for class. In fact, this contradiction is highlighted further by a unique departmental policy requiring students to anonymously report how much time they spend preparing for each lesson. Each year, students report that they are actually spending on average just half the amount of time p...
Studies in health technology and informatics, 2020
Advancements in regenerative medicine have brought to the fore the need for increased standardiza... more Advancements in regenerative medicine have brought to the fore the need for increased standardization and sharing of stem cell product characterization to help drive these innovative interventions toward public availability. Although numerous attempts have been made to store this data, there is still a lack of a platform that incorporates heterogeneous stem cell information into a harmonized project-based framework. The aim of this project was to introduce and pilot-test an intelligent informatics solution which integrates diverse stem cell product characteristics with study subject and omics information. In the resulting platform, heterogeneous data is validated using predefined ontologies and stored in a NoSQL repository. Pilot-testing was performed on nine sponsored stem cell projects conducting preclinical and intervention evaluations. The pilot-testing demonstrated the robustness of the proposed platform, by seamlessly harmonizing diverse common data elements, and the potential...
The National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) initiati... more The National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) initiative has generated extensive phosphoproteomics and proteomics data for tumor and tumor-adjacent normal tissue across multiple cancer types. This dataset provides an unprecedented opportunity to systematically characterize pan-cancer kinase activities, which is essential for coupling tumor subtypes with kinase inhibitors as potential treatment. In this work, we performed Kinase Enrichment Analysis (KEA) using a CPTAC phosphoproteomics dataset to identify putative differences in kinase state between tumor and normal tissues within and across five types of cancer. We then implemented an interactive web-portal, the ProTrack Kinase Activity Portal (ProKAP), for querying, visualizing, and downloading the derived pan-cancer kinase activity scores together with the corresponding sample metadata, and protein and phosphoprotein expression profiles. To illustrate the usage of this digital resource, w...
Phosphoproteomics and proteomics experiments capture a global snapshot of the cellular signaling ... more Phosphoproteomics and proteomics experiments capture a global snapshot of the cellular signaling network, but these methods do not directly measure kinase state. Kinase Enrichment Analysis 3 (KEA3) is a webserver application that infers overrepresentation of upstream kinases whose putative substrates are in a user-inputted list of proteins. KEA3 can be applied to analyze data from phosphoproteomics and proteomics studies to predict the upstream kinases responsible for observed differential phosphorylations. The KEA3 background database contains measured and predicted kinase-substrate interactions (KSI), kinase-protein interactions (KPI), and interactions supported by co-expression and co-occurrence data. To benchmark the performance of KEA3, we examined whether KEA3 can predict the perturbed kinase from single-kinase perturbation followed by gene expression experiments, and phosphoproteomics data collected from kinase-targeting small molecules. We show that integrating KSIs and KPIs...
Imbalance in the finely orchestrated system of chromatin-modifying enzymes is a hallmark of many ... more Imbalance in the finely orchestrated system of chromatin-modifying enzymes is a hallmark of many pathologies such as cancers, since causing the affection of the epigenome and transcriptional reprogramming. Here, we demonstrate that a loss-of-function mutation (LOF) of the major histone lysine methyltransferase SETDB1 possessing oncogenic activity in lung cancer cells leads to broad changes in the overall architecture and mechanical properties of the nucleus through genome-wide redistribution of heterochromatin, which perturbs chromatin spatial compartmentalization. Together with the enforced activation of the epithelial expression program, cytoskeleton remodeling, reduced proliferation rate and restricted cellular migration, this leads to the reversed oncogenic potential of lung adenocarcinoma cells. These results emphasize an essential role of chromatin architecture in the determination of oncogenic programs and illustrate a relationship between gene expression, epigenome, 3D genom...
Although widely prevalent, Lyme disease is still under-diagnosed and misunderstood. Here we follo... more Although widely prevalent, Lyme disease is still under-diagnosed and misunderstood. Here we followed 73 acute Lyme disease patients and uninfected controls over a period of a year. At each visit, RNA-sequencing was applied to profile patients' peripheral blood mononuclear cells in addition to extensive clinical phenotyping. Based on the projection of the RNA-seq data into lower dimensions, we observe that the cases are separated from controls, and almost all cases never return to cluster with the controls over time. Enrichment analysis of the differentially expressed genes between clusters identifies up-regulation of immune response genes. This observation is also supported by deconvolution analysis to identify the changes in cell type composition due to Lyme disease infection. Importantly, we developed several machine learning classifiers that attempt to perform various Lyme disease classifications. We show that Lyme patients can be distinguished from the controls as well as fr...
To get an improved image or to obtain any useful information from it, image processing is a metho... more To get an improved image or to obtain any useful information from it, image processing is a method of implementing any operations on an image. In the method of classifying and detection of images, this process mainly contributes to the innovation of technology. The implementation of image processing in robots had been used in earlier but with different uses. Using FPV Camera 720p OIN in the projects lets it transmits live video streaming to any device attached to it. This paper shows the robustness of image processing as it detects defects on pipes. Covering the inner external part of the pipe, the robot can pass through inside the pipe. With the accuracy of 67%, the project will be tested in different pipes and drainages for the application.
Proceedings of the ACM on Human-Computer Interaction, 2019
This paper analyzes the processes and challenges of technology repair in remote, low-income areas... more This paper analyzes the processes and challenges of technology repair in remote, low-income areas far from standard ICT repair infrastructure. Our sites of study are the fishing and farming villages of Dibut, Diotorin, and Dikapinisan in Aurora Province, Philippines, located in coastal coves against a mountain range. Residents are geographically isolated from urban areas, with the nearest peri-urban center of Baler a boat trip of several hours away, infeasible in some sea conditions. Unlike prior work in more connected rural areas, there are no local repair shops and device repair is uncommon, despite frequent breakage due to harsh conditions for electronics. The scarcity of local electronics repair limits technology access and leads to accumulation of e-waste. While prior work demonstrates that local electronics repair capability does arise in many rural areas around the world, we must also acknowledge that the successful emergence of this infrastructure depends on the intersection...
The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH Common Fund program... more The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH Common Fund program with the goal of generating a large-scale and comprehensive catalogue of perturbation-response signatures by utilizing a diverse collection of perturbations across many model systems and assay types. The LINCS Data Portal (LDP) has been the primary access point for the compendium of LINCS data and has been widely utilized. Here, we report the first major update of LDP (http://lincsportal.ccs.miami.edu/signatures) with substantial changes in the data architecture and APIs, a completely redesigned user interface, and enhanced curated metadata annotations to support more advanced, intuitive and deeper querying, exploration and analysis capabilities. The cornerstone of this update has been the decision to reprocess all high-level LINCS datasets and make them accessible at the data point level enabling users to directly access and download any subset of signatures across the entire library i...
The Motif Finding Problem is a NP-complete problem which seeks to find small conserved sites in D... more The Motif Finding Problem is a NP-complete problem which seeks to find small conserved sites in DNA sequences. Though many algorithms have been created for this problem, most typically fail on subtle motifs like Pevzner and Sze's (15,4) motif challenge. PROJECTION algorithm improves the performance of existing motif finders by using random pro-jections to provide initial estimates for the motif finder. Pre-vious efforts to parallelize PROJECTION have been done to speed up the algorithm though these efforts either use O(x 2) work complexity by using multiple comparison or employ the CPU for hashing to find initial estimates. In this paper, we present an algorithm that uses parallel hashing to improve PROJECTION's computational time.
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