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Call for Abstracts for ACS Spring 2018 Symposium ” Applications of Cheminformatics to Environmental Chemistry”

Grace Patlewicz and I have the pleasure of hosting a symposium at the Spring 2018 ACS National Meeting in New Orleans as outlined below. We believe that a presentation from you would enhance the line-up for the gathering and encourage you to consider our invitation. Our expectations are that we will have a full day of stimulating presentations and discussions regarding the application of cheminformatics to Environmental Chemistry. We sincerely hope you will consider our invitation and  submit an abstract to the CINF division listed at https://callforpapers.acs.org/nola2018/CINF.  Please confirm your intention to participate via email. Thank you in advance.

 Applications of Cheminformatics to Environmental Chemistry

Cheminformatics and computational chemistry have had an enormous impact in regards to providing environmental chemists access to data, information and software tools and algorithms. There is an increasing number of online resources and software tools and the ability to source data, perform real time QSAR prediction and even read-across analyses online is now available. Environmental scientists generally seek chemical data in the form of chemical properties, environmental fate and transport or toxicity-based endpoints. They also search for data regarding chemical function and use, information regarding their exposure potential, and their transformation in environmental and biological systems. The increasing rate of production and release of new chemicals into commerce requires improved access to historical data and information to assist in hazard and risk assessment. High-throughput in vitro and in silico analyses increasingly are being brought to bear to rapidly screen chemicals for their potential impacts and interweaving this information with more traditional in vivo toxicity data and exposure estimation to provide integrated insight into chemical risk is a burgeoning frontier on the cusp of cheminformatics and environmental sciences.

This symposium will bring together a series of talks to provide an overview of the present state of data, tools, databases and approaches available to environmental chemists. The session will include the various modeling approaches and platforms, will examine the issues of data quality and curation, and intends to provide the attendees with details regarding availability, utility and applications of these systems. We will focus especially on the availability of Open systems, data and code to ensure no limitations to access and reuse.

The topics that would be covered in this session are, but are not limited to:

 

  • Environmental chemistry databases
  • Data: Quality, Modeling and Delivery
  • Computational hazard and risk assessment
  • Prioritizing environmental chemicals using screening and predictive computational tools
  • Standards for data exchange and integration in environmental chemistry
  • Implementations of Read-across prediction
  • Adverse Outcome Pathway data and delivery

 

Please submit your abstracts using the ACS Meeting Abstracts Programming System (MAPS) at https://maps.acs.org.  General information about the conference can be found at http://www.acs.org/meetings.  Any other inquiries should be directed to the symposium organizers:

Antony J. Williams and Grace Patlewicz, National Center for Computational Toxicology, Environmental Protection Agency, Research Triangle Park, Durham, NC

Emails: williams.antony@epa.gov and patlewicz.grace@epa.gov

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Call for Abstracts for ACS Spring 2018 Symposium: “Open Resources for automated structure verification and elucidation”

I have the pleasure of hosting a symposium with Emma Schymanski at the Spring 2018 ACS National Meeting in New Orleans as outlined below. Our expectations are that we will have a full day of stimulating presentations and discussions regarding how Open Resources, specifically data and software, can support automated structure verification and elucidation. If this is an area of research for you please submit an abstract to the ANYL division listed at https://callforpapers.acs.org/nola2018/ANYL.

Open Resources for automated structure verification and elucidation

Antony J. Williams1 and Emma L. Schymanski2
1National Center for Computational Toxicology, US EPA, Research Triangle Park, Durham, NC, USA.
2Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Campus Belval, Luxembourg.
Cheminformatics methods form an essential basis for providing analytical scientists with access to data, algorithms and workflows. There are an increasing number of free online databases (compound databases, spectral libraries, data repositories) and a rich collection of software approaches that can be used to support automated structure verification and elucidation, specifically for Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS). This symposium will bring together a series of speakers to overview the state of data, tools, databases and approaches available to support chemical structure verification and elucidation. The session will cover the different databases and libraries available and examine the issues of data quality and curation. We intend to provide attendees with details regarding availability (both online and offline), utility and application of various tools and algorithms to support their identification and interpretation efforts. We will focus especially on the availability of Open systems, data and code with no limitations to access and reuse, yet reflect critically on the potential limitations and future needs of Open approaches. Case studies will demonstrate the potential for cheminformatics to enable single-structure elucidation through to high throughput, untargeted data discovery approaches. This work does not necessarily reflect U.S. EPA policy.

Emma Schymanski and Antony Williams,
Chairs of the Open Resources for automated structure verification and elucidation symposium,
ANYL Division, ACS Spring Meeting 2018, New Orleans

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Where did all of these Articles Associated With Me Come From on Mendeley

Recently I posted that Google must have changed their algorithm and as a result introduced a lot of new articles to my profile automagically that were nothing to do with me. It took work to prune them off and hopefully they do not reappear. Tonight I went through the process of updating the past few months of publications to get my Mendeley profile up to date and, lo and behold, there were a whole series of new publications that were NOT there the last time that I checked Mendeley. Interestingly they were all articles about superconducting materials as many of those that had appeared on my Google profile were. Is it possible that Elsevier is somehow sourcing the information from Scholar? Or is Elsevier sourcing these articles from within its own library? Of course the articles all have an author “A. Williams” associated with them. I have already started the process of pruning them out. Not happy…

Articles associated with A. Williams on Mendeley

Articles associated with A. Williams on Mendeley

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Mendeley Expanding my Worldwide Followers in a Big Way

I adopted Mendeley very early and was a defender of their decision to join Elsevier. I didn’t beat them up in the mediasphere for moving from the Open start-up to the publishers corporate mode. I did that myself when ChemSpider was acquired by the Royal Society of Chemistry (RSC is a charity but is also a publisher).

Over the past few weeks I have noticed new followers showing up on my profile. In the first couple of years most of my Mendeley followers were actually names I recognized from my domains of experience of cheminformatics and Nuclear Magnetic Resonance. Most of the followers were scientists whose papers I had read and whose work I was aware of. But things are now different.

I have pasted a picture below of the past month or so of new followers. I don’t recognize any of them at all and as far as I can see they are not from my domain, based on me drilling down into their profile. I cannot figure out whether these are just random followers or not but I guess I should appreciate Mendeley and Elsevier for exposing my work, and publications, to a worldwide community of new followers. I am surprised by the new international exposure! THANKS

The past few days of new Mendeley followers

The past few days of new Mendeley followers

 

 

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Increasing Noise in my Google Scholar Citations Profile

I have always been impressed with Google Scholar Citations. When I first set up my profile I was impressed with how fast the site allowed me to set up my profile (available at https://scholar.google.com/citations?user=OQEPQAAAAJ) and the overall accuracy that was evident in terms of recognizing the articles I had authored or co-authored. There was very little noise in terms of associating articles for “Antony Williams, Anthony Williams or A.J. WIlliams” (or some other combination) with my profile that were not actually my articles. As I recall maybe 3 articles overall out of about 120 at the time. I did have to add a couple of  publications that were missed but these were old, from the late 1980s.

Over the years I have been kept informed of publications that have been of relevance to my work and definitely of interest. I have also been made aware of citations to my work via email. Overall, it’s a great service.

However, of late I have become increasingly concerned regarding data quality. I have started to notice suggested co-authors showing up on my profile and emails regarding citing articles that puzzle me.

For example, today on my profile I notice the following list of suggested co-authors. Four of these are blocked in red and I have no recollection of authoring with. It is possible that these people are editors of a book that I have a chapter in but not that I recall.

Misassociated co-authors

I have rarely had to remove many associations with my profile that were incorrect but something is afoot methinks. I ended up deleting a grand total of over SEVENTY mis-associations. Some examples are below. To clarify, I know how to sleep but don’t study sleep disorders and breathing.

Ref1

I eat cream cheese but know nothing about cheese manufacture

Ref2

and I don’t know much about energy demands in Western Europe.

ref3

These articles have shown up on my profile only of late (as far as I know) and it seems that Google is casting a wider net to map more works to my profile but the dramatic DECREASE in data quality is very concerning. Whatever the decision was to do this I think it has backfired. How badly?? See below where publications are associated with my profile…that I somehow authored before I was born! I was born in 1964 so how did the 1953 article get associated with me?

ref4

The BOOK by Anna Williams from 1766 from can be purchased on eBay for less than $1000 if you want it. However, it wasn’t written by Antony Williams and should NOT be associated with my profile.

Hopefully someone associated with Google Scholar Citations sees this as input to revisit any recent changes in algorithms for associating publications with profiles.

By the way, I did take a hit, appropriately so, on my h-index when I deleted the 70 mis-associations with my name. They weren’t mine for sure!

 

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Delivering The Benefits of Chemical-Biological Integration in Computational Toxicology at the EPA

This presentation was given at the ACS Meeting in Philadelphia in August 2016.

Delivering The Benefits of Chemical-Biological Integration in Computational Toxicology at the EPA

Researchers at the EPA’s National Center for Computational Toxicology integrate advances in biology, chemistry, and computer science to examine the toxicity of chemicals and help prioritize chemicals for further research based on potential human health risks. The intention of this research program is to quickly evaluate thousands of chemicals for potential risk but with much-reduced cost relative to historical approaches. This work involves computational and data-driven approaches including high-throughput screening, modeling, text mining and the integration of chemistry, exposure and biological data. We have developed a number of databases and applications that are delivering on the vision of developing a deeper understanding of chemicals and their effects on exposure and biological processes that are supporting a large community of scientists in their research efforts. This presentation will provide an overview of our work to bring together diverse large scale data from the chemical and biological domains, our approaches to integrate and disseminate these data, and the delivery of models supporting computational toxicology. This abstract does not reflect U.S. EPA policy.

 

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Zika Virus and a hypothesis regarding the impact of Pyriproxyfen

I have been interested in the Zika Virus ever since I heard about it while visiting Brazil last year to give a talk at the Brazilian Natural Products conference. What I did not expect was the incredible surge in worldwide attention that Zika would attract. I am grateful to have been included in the work led by Sean Ekins (@collabchem) in the perspective “Open Drug Discovery for the Zika Virus” recently published on F1000Research. Up until last week the hypothesis was that Zika was a mosquito-borne disease but now the suggestion is that the disease may be related to a larvicide.

The chemical in question that is being named as the offending agent is Pyriproxyfen. I had never even heard of this chemical until a couple of days ago. At that time there was nothing on Wikipedia but, of course, it has since been updated with this

“In 2014, pyriproxifen was put into Brazilian water supplies to fight the proliferation of mosquito larvae.[2] Some Brazilian doctors have hypothesized that pyriproxyfen, not the Zika virus, is the cause of the 2015-2016 microcephaly epidemic in Brazil. [3]

Consequently, in 2016, the Brazilian state of Rio Grande do Sul suspended pyriproxyfen’s use. The Health Minister of Brazil, Marcelo Castro, criticized this step, noting that the claim is “a rumor lacking logic and sense. It has no basis.” They also noted that the insecticide is approved by the National Sanitary Monitoring Agency and “all regulatory agencies in the whole world”. The manufacturer of the insecticide, Sumitomo Chemical, stated “”there is no scientific basis for such a claim” and also referred to the approval of pyriproxyfen by the World Health Organization since 2004 and the United States Environmental Protection Agency since 2001.[4]

Noted skeptic David Gorski discussed the claim and pointed out that anti-vaccine proponents had also claimed that the Tdap vaccine was the cause of the microcephaly epidemic, due to its introduction in 2014, along with adding “One can’t help but wonder what else the Brazilian Ministry of Health did in 2014 that cranks can blame microcephaly on.” Gorski also pointed out the extensive physiochemical understanding of pyriproxyfen that the WHO has, which concluded in a past evaluation that the insecticide is not genotoxic, and that the doctor organization making the claim has been advocating against all pesticides since 2010, complicating their reliability.[2][5]

Because we live in a time of Open Data, and at a time when there is soooooo much information available on open databases, I thought I would go after any evidence-based identification of the chemical as a potential contributor to the explosion in Microcephaly.

PubChem exposes a LOT of useful data under the Safety and Hazards tab. The long-term exposure points to issues with blood and liver. FIFRA requirements are listed on PubChem and toxicity data is also available here. Reproductive toxicity is limited to reports in animals that reports

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ In /a/ developmental study in rats, a maternal NOAEL/LOAEL were determined to be 100 mg/kg/day and 300 mg/kg/day, respectively. These findings were based on increased incidences in mortality and clinical signs at 1,000 mg/kg/day with decreased in food consumption, body weight, and body weight gain together with increases in water consumption at 300 and 1,000 mg/kg/day. The developmental NOAEL /and/ /LOAEL were 100 mg/kg/day and 300 mg/kg/day /respectively/ based on the incr of skeletal variations at 300 mg/kg/day and above.

64 FR 56681 (10/21/99). Available from, as of April 28, 2003: http://www.epa.gov/EPA-PEST/1999/October/Day-21/p27398.htm
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ In /a/ developmental study in rabbits, the maternal NOAEL/LOAEL for maternal toxicity were 100 and 300 mg/kg/day based on premature delivery/abortions, soft stools, emaciation, decreased activity and bradypnea. The developmental NOAEL was determined to be 300 mg/kg/day and developmental LOAEL was /not/ … determined; no dose related anomalies occurred in the four remaining litters studied at 1,000 mg/kg/day.

64 FR 56681 (10/21/99). Available from, as of April 28, 2003: http://www.epa.gov/EPA-PEST/1999/October/Day-21/p27398.htm
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ In a 2-generation reproduction study in rats, the systemic NOAEL was 1,000 ppm (87 mg/kg/day). The LOAEL for systemic toxicity was 5,000 ppm (453 mg/kg/day). Effects were based on decreased body weight, weight gain and food consumption in both sexes and both generations, and increased liver weights in both sexes associated with liver and kidney histopathology in males. The reproductive NOAEL was 5,000 ppm. A reproductive LOAEL was not established.

64 FR 56681 (10/21/99). Available from, as of April 28, 2003: http://www.epa.gov/EPA-PEST/1999/October/Day-21/p27398.htm
Just to point out that this information, and it is valuable, is sourced from HSDB.
Pyriproxyfen reports on PubMed doesn’t seem to turn up anything about birth defects that I can find.
There is no evidence, yet, for the potential impact of this chemical on the incidence of microcephaly but the hypothesis is now out there and it will be interesting to see what happens as investigations are pursued. As yet I have no opinion….but will be watching with interest to see what comes out.

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Transform Tox Testing Challenge – Innovating for Metabolism

Scientists from EPA, NTP and NCATS have used high-throughput screening (HTS) assays to evaluate the potential health effects of thousands of chemicals. The Transform Tox Testing Challenge: Innovating for Metabolism is calling on innovative thinkers to find new ways to incorporate physiological levels of chemical metabolism into HTS assays. Since current HTS assays do not fully incorporate chemical metabolism, they may miss chemicals that are metabolized to a more toxic form. Adding metabolic competence to HTS assays will help researchers more accurately assess chemical effects and better protect human health.

Details can be found here 

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Molecular Microscopy Takes the Next Step – Monitoring a Reaction One Molecule at a Time

A new paper hit Nature Chemistry today “Reversible Bergman cyclization by atomic manipulation” (The paper will be featured on the cover of the March Issue). I have so much appreciation for what these scientists are doing. Selfishly I want to continue to applaud them for the breakthrough science that they continue to produce. I have never met the “IBM molecular microscopy” team (my chosen label) but I have had a chance to work with them on two separate occasions. One high profile one was on Olympicene, a fun story reminisced here: Olympicene From Concept to Completion. It was a lot of fun to work with scientists who found the work interesting and in reality it is NOT just a marketing story for RSC as some people mocked at the time, including some of my own colleagues! In fact, if you look at the number of articles that I have now linked (and continue to add to) on my Kudos page you will see a LOT of publications came out of the work (Kudos’ed Olympicene article plus linked articles) so not just “fun science”. In reality science is fun and real utility and understanding can come out of researching fun science, clearly.

The other chance I had to work with the team was on one of my personal interests: Structure Elucidation by NMR and the applications of Computer-Assisted Structure Elucidation (CASE) software/algorithms. The work “A Combined Atomic Force Microscopy and Computational Approach for the Structural Elucidation of Breitfussin A and B: Highly Modified Halogenated Dipeptides from Thuiaria breitfussi” combined CASE-based approaches with single molecule microscopy to elucidate new structures.

Now the team is demonstrates a reversible Bergman cyclization for the first time using atomic manipulation and verification of the products by non-contact atomic force microscopy with atomic resolution. I will let the movie below tell the story and reference you to the original paper. FASCINATING WORK. Congrats to all. How many reactions will now come under the scrutiny and validation of the team now? We will see…

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Integrating Cheminformatics and Spectroscopy to Elucidate the Structures of Natural Products

This is a talk I gave at the 5th Brazilian Conference on Natural Products as part of my “spare time” activities and to remain engaged with my passion of NMR, structure elucidation and computational spectroscopy applications

Integrating Cheminformatics and Spectroscopy to Elucidate the Structures of Natural Products

The structure elucidation of natural product structures from analytical data, specifically NMR and MS, remains a major challenge. With an enormous palette of NMR experiments to choose from, and supported by breakthrough technologies in hardware, the generation of high quality data to enable even the most complex of natural product structures to be determined is no longer the major hurdle. The challenge is in the analysis of the data. We are in a new era in terms of approaches to structure elucidation: one where computers, databases, and a synergy between scientists and algorithms can offer an accelerated path forward. Software tools are capable of digesting spectroscopic data to elucidate extremely complex natural products. Scientists can now elucidate chemical structures utilizing multinuclear chemical shift data, correlation data from an array of 2D NMR experiments and utilize existing data sets for the purpose of dereplication and computer-assisted structure elucidation. With the explosion of online data especially, in public databases such as PubChem and ChemSpider, many tens of millions of chemical structures are available to seed fragment databases to include in the elucidation process. This presentation will provide an overview of how cheminformatics and chemical databases have been brought together to assist in the identification of natural products. It will include an examination of the state-of-the-art developments in Computer-Assisted Structure Elucidation.

 

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