Joy, Yu-Yi Chu | National University of Singapore (original) (raw)
Papers by Joy, Yu-Yi Chu
https://www.medrxiv.org/content/10.1101/2020.04.10.20058222v1, 2020
The rapid spread of the Coronavirus 2019 disease (COVID-19) had drastically impacted life all ove... more The rapid spread of the Coronavirus 2019 disease (COVID-19) had drastically impacted life all over the world. While some economies are actively recovering from this pestilence, others are experiencing fast and consistent disease spread, compelling governments to impose social distancing measures that have put a halt on routines, especially in densely-populated areas. Aiming at bringing more light on key economic and public health factors affecting the disease spread, this initial study utilizes a quantitative statistical analysis based on the most recent publicly-available COVID-19 datasets. The study had shown and explained multiple significant relationships between the COVID-19 data and other country-level statistics. We have also identified and statistically profiled four major country-level clusters with relation to different aspects of COVID-19 development and country-level economic and health indicators. Specifically, this study has identified potential COVID-19 under-reportin...
Since biocomputing plays an essential role in the biological and medical fields, the catalytic fe... more Since biocomputing plays an essential role in the biological and medical fields, the catalytic features of enzymes can be utilized in medical applications as biosensor. In this study, we tried to build an enzymatic system as biosensor equipment application to measure blood sugar with sequential reactions of enzymes, which express logic output signals with latent fluorophore as a reporter. The expected biosensor will analyze three molecules sucrose, maltose and ATP existing in human blood, by adding some blood into the system consisted of various enzymes. Sucrose and Maltose will be decomposed into glucose; moreover, glucose and ATP have critical influence of glycolysis which shows one crucial reaction of human metabolism. The output signal was visualized by high throughput fluorescence that originated from the long-wavelength latent fluorogenic substrate—Salicylate hydroxylase (SHL) reaction. The experiment results of this research have showed the possibility to determine the combinations of the three important components, by setting the concentration of each input molecules to specific threshold values. Further researches are required to find out the relationship between the specific concentration and measure glucose results, especially in the medical field.
Designed molecules were successfully synthesized and showed high potency against JAK2 and HDAC1/6... more Designed molecules were successfully synthesized and showed high potency against JAK2 and HDAC1/6 in enzyme assays. Anti-proliferative effects were observed in hematological cell lines
with low micro molar IC50 values.
Hyperactivation of Janus kinases (JAKs) are strongly implicated in myeloproliferative neoplasms (... more Hyperactivation of Janus kinases (JAKs) are strongly implicated
in myeloproliferative neoplasms (MPNs), a consequence of
excessive JAK/STAT aberrant signalling. Ruxolitinib (JAK1/2)
and Tofacitinib (pan-JAK) have reached the market for the
treatment of myelofibrosis and rheumatoid arthritis,
respectively, validating the approach. Histone deacetylase
(HDAC) inhibitors regulate the acetylation status of histone
and non-histone proteins, affecting cellular functions of
neoplastic cells. Vorinostat and more recently Belinostat have
reached the market for the treatment of rare lymphomas.
However monotherapy of HDACi only demonstrates minimum
activity and combination treatment is considered necessary to
broaden application as well as to treat resistant tumors.
Polypharmacology is a new strategy to treat complex
diseases using compounds with multiple ligands which bind
to a network of interacting targets with higher efficiency and
limit drawbacks of excessive or promiscuous binding.
Combinations of separate JAK and HDAC inhibitors indicate
synergy between the two target classes, however combining
two or more drugs has many challenges in development. Here,
we report the combination of JAK-HDAC dual inhibition in a
single molecule. We chose a JAK template based on XL019
because it has specific JAK2 inhibition while being a relatively
simple structure. For HDAC inhibition, we chose to use the
well understood Vorinostat for initial proof of concept. We
have designed and synthesised highly potent dual JAK2-HDAC
inhibitors with sub-nanomolar IC50s. Furthermore, these novel
compounds are selective for HDAC6 within the HDAC family.
Target compounds have been tested in 4 solid tumor cell lines
with one compound showing sub-micromolar anti-proliferative
activity.
Consisting of four members, JAK1, JAK2, JAK3 and TYK2, the JAK kinases have emerged as important ... more Consisting of four members, JAK1, JAK2, JAK3 and TYK2, the JAK kinases have emerged as important targets for proliferative and immune-inflammatory disorders. Recent progress in the discovery of selective inhibitors has been significant, with selective compounds now reported for each isoform. This article summarizes the current state-of-the-art with a discussion of the most recently described selective compounds. X-ray co-crystal structures reveal the molecular reasons for the observed biochemical selectivity. A concluding analysis of JAK inhibitors in the clinic highlights increased clinical trial activity and diversity of indications. Selective JAK inhibitors, as single agents or in combination regimens, have a very promising future in the treatment of oncology, immune and inflammatory diseases.
Books by Joy, Yu-Yi Chu
The primary objective of clustering is to discover a structure in the data by forming some number... more The primary objective of clustering is to discover a structure in the data by forming some number of clusters or groups. In order to achieve optimal clustering results in current soft computing approaches, two fundamental questions should be considered; (i) how many clusters should be actually presented in the given data, and (ii) how real or good the clustering itself is. Based on these two fundamental questions, almost clustering method needs to determine the number of clusters. Yet, it is difficult to determine an optimal number of a cluster group
should be obtained for each data set. Hence, DNA-based clustering algorithms were proposed to solve clustering problem without considering any preliminary parameters such as a number of clusters, iteration and, etc..
Because of the nature of processes between DNA-based solutions with a silicon-based solution, the evaluation of obtained results from DNA-based clustering is critical to be conducted. It is to ensure that the obtained results from this proposal can be accepted as well as other soft computing techniques. Thus, this study proposes two different techniques to evaluate the DNA-based clustering algorithms either it can be accepted as other soft computing techniques or the results
that obtained from DNA-based clustering are not reliable for employed.
https://www.medrxiv.org/content/10.1101/2020.04.10.20058222v1, 2020
The rapid spread of the Coronavirus 2019 disease (COVID-19) had drastically impacted life all ove... more The rapid spread of the Coronavirus 2019 disease (COVID-19) had drastically impacted life all over the world. While some economies are actively recovering from this pestilence, others are experiencing fast and consistent disease spread, compelling governments to impose social distancing measures that have put a halt on routines, especially in densely-populated areas. Aiming at bringing more light on key economic and public health factors affecting the disease spread, this initial study utilizes a quantitative statistical analysis based on the most recent publicly-available COVID-19 datasets. The study had shown and explained multiple significant relationships between the COVID-19 data and other country-level statistics. We have also identified and statistically profiled four major country-level clusters with relation to different aspects of COVID-19 development and country-level economic and health indicators. Specifically, this study has identified potential COVID-19 under-reportin...
Since biocomputing plays an essential role in the biological and medical fields, the catalytic fe... more Since biocomputing plays an essential role in the biological and medical fields, the catalytic features of enzymes can be utilized in medical applications as biosensor. In this study, we tried to build an enzymatic system as biosensor equipment application to measure blood sugar with sequential reactions of enzymes, which express logic output signals with latent fluorophore as a reporter. The expected biosensor will analyze three molecules sucrose, maltose and ATP existing in human blood, by adding some blood into the system consisted of various enzymes. Sucrose and Maltose will be decomposed into glucose; moreover, glucose and ATP have critical influence of glycolysis which shows one crucial reaction of human metabolism. The output signal was visualized by high throughput fluorescence that originated from the long-wavelength latent fluorogenic substrate—Salicylate hydroxylase (SHL) reaction. The experiment results of this research have showed the possibility to determine the combinations of the three important components, by setting the concentration of each input molecules to specific threshold values. Further researches are required to find out the relationship between the specific concentration and measure glucose results, especially in the medical field.
Designed molecules were successfully synthesized and showed high potency against JAK2 and HDAC1/6... more Designed molecules were successfully synthesized and showed high potency against JAK2 and HDAC1/6 in enzyme assays. Anti-proliferative effects were observed in hematological cell lines
with low micro molar IC50 values.
Hyperactivation of Janus kinases (JAKs) are strongly implicated in myeloproliferative neoplasms (... more Hyperactivation of Janus kinases (JAKs) are strongly implicated
in myeloproliferative neoplasms (MPNs), a consequence of
excessive JAK/STAT aberrant signalling. Ruxolitinib (JAK1/2)
and Tofacitinib (pan-JAK) have reached the market for the
treatment of myelofibrosis and rheumatoid arthritis,
respectively, validating the approach. Histone deacetylase
(HDAC) inhibitors regulate the acetylation status of histone
and non-histone proteins, affecting cellular functions of
neoplastic cells. Vorinostat and more recently Belinostat have
reached the market for the treatment of rare lymphomas.
However monotherapy of HDACi only demonstrates minimum
activity and combination treatment is considered necessary to
broaden application as well as to treat resistant tumors.
Polypharmacology is a new strategy to treat complex
diseases using compounds with multiple ligands which bind
to a network of interacting targets with higher efficiency and
limit drawbacks of excessive or promiscuous binding.
Combinations of separate JAK and HDAC inhibitors indicate
synergy between the two target classes, however combining
two or more drugs has many challenges in development. Here,
we report the combination of JAK-HDAC dual inhibition in a
single molecule. We chose a JAK template based on XL019
because it has specific JAK2 inhibition while being a relatively
simple structure. For HDAC inhibition, we chose to use the
well understood Vorinostat for initial proof of concept. We
have designed and synthesised highly potent dual JAK2-HDAC
inhibitors with sub-nanomolar IC50s. Furthermore, these novel
compounds are selective for HDAC6 within the HDAC family.
Target compounds have been tested in 4 solid tumor cell lines
with one compound showing sub-micromolar anti-proliferative
activity.
Consisting of four members, JAK1, JAK2, JAK3 and TYK2, the JAK kinases have emerged as important ... more Consisting of four members, JAK1, JAK2, JAK3 and TYK2, the JAK kinases have emerged as important targets for proliferative and immune-inflammatory disorders. Recent progress in the discovery of selective inhibitors has been significant, with selective compounds now reported for each isoform. This article summarizes the current state-of-the-art with a discussion of the most recently described selective compounds. X-ray co-crystal structures reveal the molecular reasons for the observed biochemical selectivity. A concluding analysis of JAK inhibitors in the clinic highlights increased clinical trial activity and diversity of indications. Selective JAK inhibitors, as single agents or in combination regimens, have a very promising future in the treatment of oncology, immune and inflammatory diseases.
The primary objective of clustering is to discover a structure in the data by forming some number... more The primary objective of clustering is to discover a structure in the data by forming some number of clusters or groups. In order to achieve optimal clustering results in current soft computing approaches, two fundamental questions should be considered; (i) how many clusters should be actually presented in the given data, and (ii) how real or good the clustering itself is. Based on these two fundamental questions, almost clustering method needs to determine the number of clusters. Yet, it is difficult to determine an optimal number of a cluster group
should be obtained for each data set. Hence, DNA-based clustering algorithms were proposed to solve clustering problem without considering any preliminary parameters such as a number of clusters, iteration and, etc..
Because of the nature of processes between DNA-based solutions with a silicon-based solution, the evaluation of obtained results from DNA-based clustering is critical to be conducted. It is to ensure that the obtained results from this proposal can be accepted as well as other soft computing techniques. Thus, this study proposes two different techniques to evaluate the DNA-based clustering algorithms either it can be accepted as other soft computing techniques or the results
that obtained from DNA-based clustering are not reliable for employed.