Ryan's Blog on NMR Software

What's New in Version 11- Improved 1D NMR Structure Verification Accuracy

Automated structure verification using ACD/Labs software is a method that compares the chemical shifts, intensities, and multiplicities of signals in experimental NMR spectra with those from a predicted NMR spectrum with a proposed structure.

Naturally, in order for this process to be effective the chemical shift prediction, multiplet characterization, and integration measurements must be accurate. This process is described in detail in a 2006 publication in MRC.

As mentioned in the previous post, in version 11 the automated multiplet analysis
algorithm in ACD/Labs software has been significantly improved.

The purpose of this post is to show you how much the improvements of the automated multiplet analysis algorithm in version 11 impacts the performance of automated verification of ¹H NMR spectra.

The following results compare the verification improvements in version 11 based on the multiplet analysis enhancements ONLY. In version 11 we made several other improvements in NMR prediction and analysis, and I will get to them in a future post. For now:

For this study, two different data sets each consisting of the ¹H NMR spectra of 30 samples and the correct chemical structures were automatically processed, analyzed, and evaluated by the software.

Test Set 1- A set of 30 spectra and their respective chemical structures with reasonably good signal to noise:

Test Set 2- A set of 30 spectra and their respective chemical structures with lower signal to noise:

As you can see clearly, the improvements in multiplet analysis in version 11 heavily impact the performance of automated NMR verification of ¹H NMR data in both datasets. Based on the dataset used for this study, the software (employing the version 11 multiplet analysis algorithm) was able to correctly confirm the consistency between the proposed chemical structure and the experimental spectrum ~60% of the time in both datasets.

For a real world application of this system, check out a previous post that described Anthony Macherone's workflow at ASDI (and a link to his presentation).

The next questions is, "If you use more data, how well does this system perform?"

A future post will describe a study that highlights the latest performance statistics of a "combined verification" approach that can automatically identify  correct and incorrect chemical structures based on their 1D ¹H and 2D HSQC NMR data. This system was described in a 2007 publication in MRC.

Stay Tuned.

What's New in Version 11- Improved Multiplet Analysis

In case you didn't know, version 11 of ACD/Labs software was released in November of 2007.

While there are several updates to the software over the course of a year, a major new version of each of our NMR products is released on an annual basis.

Over the next couple of weeks on this blog, I will try to mix in some new features and improvements that have been implemented in version 11.

First up, I'll talk a bit about improvements in the automated multiplet analysis algorithm in ACD/1D NMR Assistant, ACD/1D and 2D NMR Processor, ACD/1D and 2D NMR Manager, and ACD/1D and 2D NMR Expert.

For those unfamiliar with this process, automated multiplet analysis refer to the use of a software algorithm that automatically characterizes coupling patterns and extracts coupling constants from multiplets in an NMR spectrum.

The most popular application of this feature is that it provides an incredibly fast way of generating a formatted multiplet report for patents and publications:

¹H NMR (400 MHz, DMSO-d₆) d ppm 2.34 (dd, J=15.97, 8.06 Hz, 1 H) 2.64 (dd, J=16.05, 5.35 Hz, 1 H) 3.81 (tt, J=7.71, 5.33 Hz, 1 H) 4.47 (d, J=7.47 Hz, 1 H) 4.87 (d, J=5.13 Hz, 1 H) 5.68 (d, J=2.20 Hz, 1 H) 5.88 (d, J=2.34 Hz, 1 H) 6.58 (dd, J=8.13, 1.98 Hz, 1 H) 6.68 (d, J=8.06 Hz, 1 H) 6.71 (d, J=1.91 Hz, 1 H) 8.

So how well does this automated algorithm perform in Version 11?

Significant development efforts were put into improving the automated routine for Version 11 and I will present the results of a direct comparison to version 10 of the software.

For this study, two different data sets each consisting of the ¹H NMR spectra of 30 samples were studied (~250 multiplets in total).

Test Set 1- A set of 30 spectra (~250 multiplets) with reasonably good signal to noise:

We ran the automated multiplet analysis routine on all 30 spectra and got the following results in Version 10:

In version 10, 53% of the multiplet patterns in the spectra for the 30 samples were correctly defined, 32% were undefined, leaving 15% that were incorrectly defined. Multiplets that are termed as undefined are simply given a "m" designation for multiplets. In standard practices and manual analysis the "m" designation is often assigned by users to multiplets with unresolved peaks, often due to strong coupling.

Version 11 Results:

As you can see, while the number of correctly defined multiplets increased by 5%, the most notable observation is the reduction of incorrectly defined multiplets from 15% to 1%.

Test Set 2- A set of 30 spectra (~250 multiplets) with lower signal to noise:

 

Version 10 Results:

Version 11 Results:

As you can see in the second study, we did sacrifice some correctly defined multiplets (6%), but we were able to reduce the number of incorrectly defined multiplets significantly from 14% to 3%.

So how does this improved accuracy impact the end user?

First of all, this will result in significant time savings with more accurate automated multiplet analysis and report creation for spectroscopists' and chemists' patents, publications, etc.

But perhaps of more scientific relevance, is that improved automated multiplet analysis heavily impacts both the performance of automated structure verification in ACD/1D and 2D NMR Expert, as well as the structure verification algorithm included in ACD/1D NMR Assistant.

How much impact are we talking about here?

Stay tuned, it will be the topic of my next post.

If you are currently using Version 11, try it out, and share your results in the comments section.

NC Science Blogging Conference

I had the opportunity to attend the North Carolina Science Blogging Conference last week in Research Triangle Park, NC.

I was rather surprised to meet a variety of people from various scientific disciplines who are actively blogging. Everything from  Psychology to Deep Sea Diving to Coast Guard Blogging to Chemistry.

There were certainly lots of interesting discussions and debates.

One of the highlights of the conference for me was a presentation by Jean-Claude Bradley who shared (literally) some of the fascinating work he has been doing in open notebook science using a variety of different online tools.

If you are interested in learning more, you're lucky, because Jean-Claude has provided access to his presentation online (Click on the screen below to start the video):

Jean-Claude is also the author of an excellent blog entitled, the Useful Chemistry blog that represents his open source chemistry project.

Note: If you are receiving this post via email, you will have to come to the blog to view the presentation.

More on Indirect Covariance

Gary Martin has added a comment to an earlier post I wrote on Indirect Covariance and was kind enough to post an updated publication list on this topic. I have simply copy and pasted his comments in this post to provide more exposure to his list:

Ryan, it has been a while since you updated the publication list on indirect covariance methods, so I thought it appropriate to do that with a post:

F. Zhang and R. Bruschweiler, J. Am. Chem. Soc., 126, 13180 (2004).

K. A. Blinov, N. I. Larin, M. P. Kvasha, A. Moser, A. J. Williams, and G. E. Martin, Magn. Reson. Chem., 43, 999 (2005).

K. A. Blinov, N. I. Larin, A. J. Williams, M. Zell, and G. E. Martin, Magn. Reson. Chem., 44, 107 (2006).

K. A. Blinov, N. I. Larin, A. J. Williams, K. A. Mills, and G. E. Martin, J. Heterocyclic Chem., 43, 163 (2006).

K. A. Blinov, A. J. Williams, B. D. Hilton, P. A. Irish, and G. E. Martin, Magn. Reson. Chem., 45 544 (2007).

W. Schoefberger, V. Smrečki, D. Vikić-Topić, and N. Müller, Magn. Reson. Chem., 45, 583 (2007).

G.E. Martin, P. A. Irish, B. D. Hilton, K. A. Blinov, and A. J. Williams, Magn. Reson. Chem., 45, 624 (2007).

G.E. Martin, B.D. Hilton, P.A. Irish, K.A. Blinov, and A.J. Williams, J. Heterocyclic Chem., 44, 1219 (2007).

G.E. Martin, B.D. Hilton, P.A. Irish, K.A. Blinov, and A.J. Williams, J. Nat. Prod., 70, 1393 (2007).

G.E. Martin, P. A. Irish, B. D. Hilton, K. A. Blinov, and A. J. Williams, Magn. Reson. Chem., 45, 883 (2007).

B. Hu, J.-P. Amourex, and J. Trebose, Solid State Nuclear Magnetic Resonance, 31, 163 (2007).

G.E. Martin, B.D. Hilton, P.A. Irish, K.A. Blinov, and A.J. Williams, J. Nat. Prod., 70, 1966 (2007).

D. A. Snyder, Y. Xu, D. Yang, and R. Bruschweiler, J. Am. Chem. Soc., 129, 14126 (2007).

G.E. Martin, B. D. Hilton, K. A. Blinov, and A. J. Williams, Magn. Reson. Chem., 46, 138 (2008).

G.E. Martin, B.D. Hilton, K. A. Blinov, and A. J. Williams, J. Heterocyclic Chem., 45, in press (2008).

This is the list I currently have. Note that this list does not contain additional papers that pertain to homonuclear covariance processing methods. I don't have that list of publications handy that I can cut and paste into this post.

Thanks Gary!

Manuals, Technical Notes, Movies, Doh!

What kind of supporting documentation do you prefer to follow when you attempt to learn a new piece of software?

The inspiration for my last post on Ease of Use came from a discussion I had with my colleague Arvin Moser. Arvin has spent many years with ACD/Labs as a Technical Support Specialist for ACD/Labs and is now an Application Scientist. Arvin knows the learning curve of ACD/Labs software very well.

Following my post last week Arvin and I continued an interesting discussion about user manuals and their usefulness. Arvin was kind enough to summarize our conversation for me and here it is:

Ask anyone who buys a piece of software for their computer whether they feel better that software comes with a manual and chances are everyone will say YES. The thought of having a manual is like a security blanket in case things go bad.

http://en.wikipedia.org/wiki/Instruction_manual_%28computer_and_video_games%29

Since there are so many variations of manuals, let me list what I deem to be a manual, or at least what I’ve seen that comes with a piece of software. There are the instruction manuals, the tutorials, the guides, and reference manuals. They can be stored on a DVD, online and/or in hardcopy form. Online manuals are a convenient way for those users who cannot seem to find older or lost manuals. Electronic manuals have the advantage of allowing key word searching and thus narrow done the bit of information you really need.

Taking it a step further, how many people actually spend the time to read the manual? I doubt that number would be very high especially if it spans more than 20 pages. Most people like to install software and run with it. How many people do you know that have read the manuals that come with Microsoft Excel 2000, 2002, 2003 and 2007? Not a very exciting read, I'm sure.

To simplify matters, many pieces of software come with a quick guide sheet that holds the crucial instructions on a single piece of paper. Not bad and probably the easiest thing a computer company can do to help out its users.

How about those people who do not like to read or can’t read? Then what? Movies are a great way to teach visually what sometimes cannot be easily explained with words and diagrams. Interactive movies add the benefit of enabling viewers to test what they learn without messing up the software directly. Other things that come to mind are word of mouth from an expert user (i.e. Live Help http://www.skype.com/intl/en/share/buttons/), technical support, user forums, and on-site or online training sessions. In a society built on diversity, the key seems to be to provide venues to satisfy as many people as possible.

There are so many possibilities. Let me pose this question:

Should a company that produces software offer all these facets?

What facet do you prefer?

Feel free to add your comments on the blog. 

Ease of Use

As a software company I believe that we have a responsibility to our users to make our products easy to use. A significant amount of time should be (and is) spent every year evaluating how our software can be more user-friendly.

If you browse around the web and look at various software packages, you will almost always find product descriptions that claim the product is, “easy to use”. 

But what exactly does this mean? 

What makes a software product easy to use?

I absolutely think that a software package should be intuitive, and that it should be easy to understand out of the box. 

The reviews I hear regarding ACD/Labs software are generally positive. I have heard from most users that our software is very intuitive and easy to use. But of course I have heard the other side as well and in many cases, the comments were justified. No software package is perfect.

Many of our users over the years have told me that the ideal software product is one where they don’t need to read the manual or watch a movie before using. They should be able to hit the ground running with it.

I would most definitely agree, but the long tail of software has made this more and more difficult and has somewhat changed the game. Software has of course exploded over the years, so the challenge now is how to develop the easy to use, one size fits all software package. 

I have to be honest; I think it is near impossible. Why? Because ease of use is subjective. Quite simply, users have been exposed to too much software. There are so many options, so much variety, so many different ways to do things in a software package. I’m not saying this is a bad thing, but it certainly introduces a bigger challenge for product managers and software developers who are trying to develop the “easiest to use” package. 

As a result what tends to happen is that with many options, people end up using the software they have access to. It might not be the best software for what they are trying to do, but it’s the software installed on the computer in the NMR laboratory or the freeware that can be downloaded from the web. They get so used to the intricacies within this particular package, that when something new comes along that may be more suitable for their work they don’t bother committing to it because they are used to the same routine. Old habits die hard.

People are busy and learning a new piece of software that may or may not be useful is not necessarily their job.

However, in my opinion, individuals who do this are committing an awful disservice to themselves.

The first impression on a new package is often that it is hard to use. But is it hard to use? Or is it just unfamiliar? 

I am not suggesting that there is no such thing as hard-to-use software. It’s out there, in every industry. But I think that it goes both ways. While it is the responsibility of the product manager and software developer to work as hard as they can to make their packages intuitive and easy to use, users also owe themselves the responsibility to understand the benefits that a specific software package provides and make a conscious attempt to familiarize themselves with the new workflows, interfaces, etc.

If a company is going to charge for their software, my hope is that significant attempts have been made during development to make it easy-to-use. But that term is hard to define and not an easy task. 

I hope that over the last 7 months and 54 blog posts I have helped current users keep up to date on ACD/Labs NMR software, but have also given new users reasons to evaluate our software and commit to reaping the benefits that it can provide. 

Note: This unfamiliarity issue of course isn’t anything new and it’s not just a software issue. It’s an issue for the developers of mp3 players, cell phones, remote controls, computers, and cameras. Don’t believe me? Next time you are on vacation ask a fellow tourist to take a picture for you and hand them your camera. I guarantee that they respond with, “What do I do?” 

Hint: It’s the button on the top right hand corner ;)

ACD/1D NMR Assistant Part 3-Structure Verification

The movie in this post will highlight the new structure verification feature available in ACD/1D NMR Assistant.

In the last posting, I highlighted the multiplet assignment preview (MAP) that provides users with input during the assignment process.

The purpose of this posting is to highlight another feature that is very unique in the NMR software world. ACD/1D NMR Assistant includes a structure verification algorithm that can help users quickly verify the consistency between a proposed chemical structure and a ¹H NMR spectrum.

As you will see in the movie, in addition to providing a simple verification result, the software will automatically assign experimental multiplets (based on their chemical shifts, multiplet properties, and integration values) to protons in the chemical structure. Finally, if any inconsistencies exists they are clearly labeled on the structure and a detailed explanation is provided to focus the user on the specific area on the spectrum where the inconsistency exists.

If you can't get the above video to work, or if you want a bigger version, click here to watch the demonstration of the structure verification feature in ACD/1D NMR Assistant.

Once again, this demonstration is for illustration purposes. 

ACD/1D NMR Assistant Part 2- Assigning NMR Data

The movie below (if you receive this by email you will have to come to the blog) highlights the unique Multiplet Assignment Preview available in ACD/1D NMR Assistant.

This feature helps users evaluate potential assignments by considering the chemical shifts, multiplet properties, and integration values of experimental multiplets in the spectrum.

Just another reason to embrace NMR software. A piece of paper can't do this:

If you can't get the above video to work, or if you want a bigger version , click here to watch the demonstration.

The above example is just for illustration purposes. The best way to evaluate the software on your own data is to go to the ACD/Labs website and request a free trial.

Stay Tuned....next up, the structure verification algorithm in ACD/1D NMR Assistant!

The Simpsons

No, I am not talking about Bart, Homer, or Marge.

I am talking about Andre and Myrna Simpson:

Congratulations to both Andre and Myrna for being recognized by the acclaimed Toronto Star as one out of ten people, bands, or teams to keep an eye out for in 2008.

Link to Story

Toronto is a huge city with rising stars everywhere, and it is nice to see a couple of chemists getting the recognition they deserve.

Andre and Myrna are good friends with ACD/Labs and close collaborators on a number of interesting projects over the years. Andre has also presented at our seminars multiple times at conferences around the globe.

Congratulations again to Myrna and Andre!