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ASMS 2018: Exhilarating and exhausting

The American Society of Mass Spectrometry annual conference represents my one sure visit to the United States each year.  What is it about this meeting that keeps bringing me back across the Atlantic Ocean?  What makes this gathering feel like an academic home?

Early Days

My first encounter with ASMS took place in 1998, when I attended the annual conference in Orlando.  During this and other early years of the conference, I made it my goal to eat only free food during the four days of the conference.  I remember ice cream breakfasts from a vendor at this first meeting!  Being notoriously frugal did my waistline no favors, but then I was skinny as a rail during graduate school.

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Prof. Pevzner, from his early days as a Wild West sheriff

My Ph.D. project involved the creation of a automated sequence tag inference engine from low-resolution tandem mass spectra of peptides.  That meant I had one particular talk on my agenda for ASMS 1998.  I listened with rapt attention to talk WOF 3:10 given by Pavel Pevzner (then a scientist at Millennium Pharmaceuticals) describing his SHERENGA software: “Automated De Novo Peptide Sequencing.”  I remember introducing myself to him after his talk.  When I mentioned my project, I remember poking in that we were competitors!  I was a frightfully competitive guy back then.  I am grateful that Pavel let the comment pass; in the two decades since that meeting he and I have become friends.

I feel I must mention ASMS 2004, the year that John Yates, III won the Biemann Medal, which I consider to be mass spectrometry’s highest award.  The conference was held at Nashville, TN, which was lovely given that I was a post-doc at Oak Ridge National Laboratory, just four hours down the interstate.  I arrived at the conference to learn that Steve Gygi, a friend of mine from graduate school, had played an epic prank on John and me at one of the preliminary meetings.  A student of his had captured a video of John and me encouraging people to get out onto the dance floor at a Keystone Symposium.  Steve had used the video in a research talk to show that while John was an expert in biochemistry, analytical chemistry, and bioinformatics, he couldn’t dance!

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…of which the less said, the better

Professional Integration

To attend a yearly conference is one thing, but becoming part of its organization is quite another.  After I joined the faculty of Vanderbilt University in 2005 as an assistant professor, I decided that ASMS was the organization that felt most like “home” to me, and I began paying my dues yearly rather than haphazardly on the years I planned to attend the conference.  I became familiar with a growing number of its luminaries, both through the senior scientists with whom I collaborated and through smaller meetings, such as the Association of Biomolecular Resource Facilities and the United States Human Proteomics Organization.  Happily, I gained a reputation as an energetic speaker who could make mass spectrometry informatics seem more approachable.

My three biggest public roles within ASMS have all been drawn from the field of mass spectrometry informatics.  I feel deeply honored to have twice selected the speakers to appear in panels on the informatics of identification.  My second big involvement was with the Bioinformatics Interest Group.  After the main panels on each full day of the conference, ASMS features workshops for interest groups, running from 5:45 to 7:00 PM.  Since the conference attendees tend to exhaustion after such busy days, the workshops function best when they feature passionate speakers that interact quite a lot with the audience.  I am certainly not ashamed to stand outside the meeting room, inviting absolute strangers to join our group!  I enjoyed my moments as Donahue, running between different members of the audience with the microphone.

My biggest engagement, however, has been a long-running ASMS short course.  In 2011, Alexey Nesvizhskii, Nuno Bandeira, and I offered “Bioinformatics for Protein Identification” for the first time.  In this two-day short course (on the Saturday and Sunday preceding the conference), we introduced the algorithms that enable protein identification for newcomers to proteomics.  Happily, the course drew a good response, and we have now run the short course for eight consecutive years!  It’s a lot of work, and it makes each ASMS visit six days rather than four, but I really draw a lot of satisfaction from working with the participants.

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The 2018 class

ASMS 2018: San Diego

What made this year such a busy program?  I would start with the fact that I completed my Ph.D. at San Diego, and I had many friends to visit while there!  I was very grateful to visit with friends from the “Darkstar” science fiction, gaming, yoga, and movie-making club; I hadn’t seen many of them for fifteen years!  I was also happy to see Ben Winnick, a friend of mine since my undergraduate years at the University of Arkansas.  It’s humbling to think I have known him since 1997.  These social calls complemented the professional friendships I was able to renew at the conference.

Since John Yates has made his home in San Diego since 2000, I was also glad to attend the reunion dinner he organized on the Saturday before the conference.  I was sitting down to dinner with my extended family of 200 friends, a bit worn out from running the first day of our short course, when I learned that the first speaker for the event had dropped out due to illness.  I was soon penciled in to replace him!  I frantically scribbled some notes while eating so that I could share some of my favorite stories from the early Yates Lab.  I was glad I could make people laugh!

Although I was not part of this year’s bioinformatics interest group, I was included as a speaker for the Analytical Lab Managers Interest Group under Emily Chen and David Quilici at their Monday evening workshop.  I emphasized the methods core lab managers need to incorporate “Big Data” into their work, emphasizing data repository use and careful statistics.  I slumped into my hotel bed directly after this talk; I had been yammering about something or other almost continuously for three straight days.

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Dave goes contrarian.

Wednesday put me right back on stage.  I was slated for a mock debate over at the Informatics Hub.  I was paired with my friend Juan Antonio Vizcaino (responsible for PRIDE repository); he would argue that Big Data was transforming proteomics, and I would argue that Big Data was creating more problems than it was worth!  It’s true that I have some doubts about the value of Big Data practices to date.  I hope my talk caused participants to think about good strategies for its incorporation.

Of course, the “work” that most conference attendees incur still awaited me.  I had submitted a poster reporting work I have conducted in agricultural proteomics with the University of the Western Cape.  We created an ortholog mapping table via BLAST that allowed us to determine which protein in sorghum mapped to which protein in maize.  We then used the mapping table to re-align our spectral count table so that the counts for each ortholog pair appeared on the same row.  This means our statistical model can look for differences between our “wet” and “dry” cohorts in both species, simultaneously!  I look forward to writing that paper.  My poster had been slated for Thursday, so I dutifully stood beside my A0 format poster throughout the morning and into the early afternoon.  I was glad to see that the poster hall was not completely deserted, even on the last day.

I am grateful to the people that launch the annual conference for ASMS each year.  It’s wonderful to gather with friends and see what each of us has created in the course of our work!

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HUPO-PSI 2018: Dave’s takeaways

I have now attended three HUPO-PSI (Human Proteome Organization Proteomics Standards Initiative) meetings: Ghent, Beijing, and Heidelberg.  As an early skeptic about the standard data formats for mass spectrometry, I confess I have substantially revised my opinion on the usefulness of HUPO-PSI.  I have now served as the Quality Control Working Group chair for two full years, and I feel I understand quite a lot more of what these meetings accomplish.

Who is HUPO-PSI?

HUPO-PSI may receive less name recognition than the formats that they have made possible.  Thousands of biological mass spectrometrists have used the mzML format, frequently employing ProteoWizard software to produce it.  The mzML format, then is probably HUPO-PSI’s most conspicuous success.  This format, though, was not the first XML-based attempt to capture proteomics data.  We would probably point to mzXML for that.  Actually, mzML wasn’t even the first file format canonized by HUPO-PSI for this purpose!  We would point to mzData for that.  Because HUPO-PSI was humble enough to seek the input of the mzXML team, a far more fully-fledged format, mzML, could be produced by merging the best aspects of mzData and mzXML.  I also see a huge splash from the Molecular Interactions side of HUPO-PSI, though I have always associated with the mass spectrometry side instead.

HUPO-PSI has its share of detractors, as well.  The group has placed quite a lot of emphasis on XML as the preferred “persistence” (mode of long-term information storage), though its formats have occasionally been translated to other strategies for long-term storage, such as the HDF5 scalable technology suite.  A consequence of embracing XML is that researchers see their data storage needs increase significantly; we frequently see that the mzML produced from a Thermo RAW file increases in size even as it reduces the amount of information it contains through “peaklisting.”  As a consequence, some of the groups within HUPO-PSI have invested effort in more streamlined options for data storage, such as the tab-delimited “mzTab” format, now undergoing an expansion to a wide variety of analyte types.  The team of which I am part, the Quality Control Working Group, is looking at another structural strategy called JavaScript Object Notation or “JSON” for compactly relating information.

Two topics have mystified me more than any others about the operation of HUPO-PSI.  The first is the reliance on a “CV” and “ontology.”  Controlled Vocabularies are essentially sets of terms that have been rigorously defined for use in reporting a kind of information.  An ontology relates these terms together, for example through “IS_A”, “PART_OF,” “HAS_PART,” and “REGULATES” relationships employed in the Gene Ontology.  HUPO-PSI makes use of ontologies that have been defined for other efforts, such as the Units of Measurement Ontology created by European Bioinformatics Institute and Phenotype and Trait Ontology.  It also maintains its own set of controlled vocabularies, such as the PSI-MS.  For my quality control to create a HUPO-PSI compatible format means connecting into these information resources rather than “reinventing the wheel” with an altogether new ontology.

The second topic that mystifies me is the “Document Process.”  Once a working group has beaten all the problems they can find from a proposed file type (a schema, or format to store the information, along with a CV that defines key terms for that file type), they submit the package to the document process, wherein more experienced standards creators draw attention to potential problems and external reviewers evaluate the extent to which that format meets the needs of the community for which it is intended.  I will learn a lot more about the Document Process when our proposal is ready for this group!

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Despite his expression, Bunsen would certainly approve!

Meeting Outcomes

The mzML format seems very stable and very capable in its version 1.1.0.  Mass spectrometry technologies, however, are always improving!  For the last decade and more, ion mobility technology has been maturing in technology development laboratories, and a few mass spectrometry vendors now offer instruments that incorporate this separation technology.  The mzML CV and schema, however, has had somewhat patchy support for the information from this separation.  At this year’s meeting, Eric Deutsch convened a small group of people to discuss the best way to support this technology within mzML, ideally without forcing a major update in the format.  Hans Visser of Waters Corporation has made a lot of contributions on this score, and Matt Chambers (a wunderkind whose company I enjoyed during my decade at Vanderbilt) had offered some feedback on how to incorporate this information.  Our meeting at HUPO-PSI helped set us on a course for formal support for ion mobility!

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I am grateful for the Ph.D. students and recent grads supporting our effort!

The HUPO-PSI Quality Control Working Group

I was really proud of the Quality Control Working Group.  I assigned us all a bit of homework for this meeting.  Three committee members create tools that generate quality metrics; all of us were assigned the task of creating a mock-up of the qcML we thought our software should produce.  One of us produced a database for storage of quality metrics; he was tasked to demonstrate what a qcML holding an analysis of these metrics should look like.  As a result, this meeting was far more concrete about what we need to do to finalize this format.  In particular, we grappled with the challenges of embedding information in JSON format within an XML wrapper.  Our consideration of complex data structures for particular metrics, such as three-dimensional matrices, is now much more applied in nature.

The field of proteomics needs to improve its ability to communicate issues of quality control.  There’s a perception of irreproducibility that hangs over the field.  While there is some basis in reality for these reproducibility claims, a fair bit of the problem is that researchers shy away from discussing quality issues in their papers.  A Ph.D. student in Shanghai has been heading the Quality Control Working Group recommendations for “MIAPE-QC:” the Minimal Information About a Proteomics Experiment for Quality Control.  I was sad that she could not attend the meeting due to grad school requirements, but a colleague of hers from Beijing presented the current state of the MIAPE-QC document.  We had a really good conversation about it, but I think our recommendations were a bit garbled on their way back to her; she was discouraged by our feedback and felt we were arguing for her to start over.  We’re working to clear up the confusion.  We will support her valuable efforts in educating our community.

Next stop: Cape Town?

As the meeting drew to a close, I put on my presenter hat one last time.  It was time to state my case for hosting the next HUPO-PSI at Cape Town!  Several different sites are bidding to host: Adelaide, Tokyo, San Diego, and Cape Town are all in the mix.  I started by taking the bull by the horns.  Cape Town may seem very far away, but it is actually in the same time zone as Heidelberg!  Flying from New York City is pretty rough, though, with a flight time of almost 15 hours.  My friend Eric Deutsch would have one of the worst routes since he is coming from Seattle.  Still, South Africa is seeing good growth in mass spectrometry, and we would love to see more of its laboratories corresponding with HUPO-PSI.  I highlighted some of the lovely attractions and hosting sites that we might visit as a group.  Hopefully, the steering committee will see its way to Cape Town in the near future!

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The HUPO-PSI Steering Committee enjoys dinner.

Did OMICS International make me a legitimate offer?

In today’s post, I want to illustrate a conundrum that faces many scientists in clearing their crowded email inboxes.  In brief, I was asked to contribute a manuscript on short notice for publication in a journal.  The closer I looked at the offer, though, the more I doubted that it was legitimate.  I would be curious to hear your evaluation in the comments!

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by oksmith at Open Clip Art

March 21, 2018  Initial solicitation

The ball began rolling with this message from the editorial assistant of a journal (if you don’t mind, I will omit the particular journal title):

We are in shortfall of one article for successful release of Volume 11, Issue 3. Is it possible for you to support us with your transcript for this issue before 5 April, 2018? If this is a short notice please do send 5-6 pages Short commentary or Mini review, and hope that a 5 pages article will not take much time for an eminent like you.

We are confident that you will always be there to support us.

Looking forward for your positive response.

Promising, right?  I think most professors have a few ideas that they’d like to get out in the literature that might not be big enough for a full research article but are still worth jotting down.  This solicitation offered quite a lot of latitude; if I wanted to write a position paper on a controversial issue in my field, this might be a nice vehicle. (For example, I might use the title “Can we trust the False Discovery Rates from Open Search?”)

Let’s pause a moment to consider the language of this request more closely.  Did you notice the flattery?  I am not just some random prof, I am an “eminent!”  Do you see the sense of shared struggle in the phrase “always be there to support us?”  At this point, you are probably wondering what my prior interactions with this publisher look like.  The answer is essentially zero.  I have never knowingly published a manuscript with this publisher, and I am sure I have never published a manuscript with the journal in question.  As I look at the Editorial Board Membership for the journal, however, I see many people with whom I have collaborated over the years.  This is unsurprising, since the Editorial Board enumerates 90 senior researchers!  A friend of mine in HUPO-PSI, however, serves as one of four Executive Editors for the journal.  Could this request be coming from her office?

omics-logoOMICs International has a checkered standing with me.  My mailbox is always littered with requests to attend conferences, and a fair few of these come from this group.  Their webpage contains a laundry list of meetings on almost every conceivable topic.  The typical mechanism is that organizers find an exotic location researchers might want to visit, round up a group of eminent people who agree to be used in publicity, and then they sell tickets to junior researchers who pay the steep registration fee and travel costs from grants.  I essentially never attend conferences unless my travel is paid by the conference, so these have been of little interest to me.  I eventually managed to unsubscribe from this continuing barrage.  Unlike many organizers, OMICs International seems to honor unsubscribe requests.

Regardless of who is asking, I need to know that publishing with the journal would be worthwhile.  It is a significant “ask” to marshal one’s team to knock out a manuscript in so short a period.  A quick look at the calendar showed only ten working days from the date of the request to the due date (South Africa has a four-day weekend for Easter, coinciding with the end of term for learners– the Monday after Easter is “Family Day”).

logo_footerI discussed the journal in question with others.  My friend (and Dean) Ndiko at UWC used the Scimago Journal and Country Rank website to interrogate its reputation.  Scimago reported an “H-Index” of 14 for the journal.  My most commonly targeted journal is Journal of Proteome Research, from the American Chemical Society.  By comparison, Scimago reports its H-Index to be 133.  A very heavy hitter like Nature Biotechnology rates even higher, with an H-Index of 361.  Scimago also related, however, that the OMICs International journal had not been tracked since 2014, so I understood a potential reason that they were unable to populate their next issue with enough submissions!  This left me with the impression that my investing effort in a publication with this OMICs International journal would be like dropping a pebble into the ocean, with hardly a splash.

support-resources-logo-pubmedI had nearly decided to blow off the request when my colleague Helena reminded me that graduate students at my university can receive a “bounty” of 2000 Rands for authoring a paper in a listed journal.  Since my student seemed quite gung-ho about knocking out a rapid manuscript, I decided that the criterion I most cared about would rule the day.  Can people search the OMICs International journal in NIH PubMed?  Yes!

March 27, 2017  Caught short

We rapidly set the battle plan in motion for our quality control manuscript in response.  I sent word to the journal office that I intended to write a paper for them and gave them a draft title.  Our team of four began marshaling data sets, analyses, and text into a Google Doc.  We got excited about the idea we had for a new application of quality metrics in proteomics.

Something started nagging at me after I read the instructions for authors on the journal website.  First, the variety of formats considered by the journal was essentially all-encompassing: “original articles, reviews, abstracts, addendums, announcements, article-commentaries, book reviews, rapid communications, letters to the editor, annual meeting abstracts, conference proceedings, calendars, case-reports, corrections, discussions, meeting-reports, news, obituaries, orations, product reviews, hypotheses and analyses.”  Essentially they’d publish anything.  One of the possibilities I was seeking, however, was not given on this list: a protocol article would let us provide training to readers on how to carry out a particular quality control process, one that I had taught in 2017 at Moscow.  I wondered if our battle plan for the manuscript would fly with the journal.

My bigger concern, however, stemmed from the text on the instructions for authors that detailed “Article Processing Charges.”  When I returned to the initial request, I noted that charges were entirely omitted from the message.  I wrote them right away to confirm that because this was an invited manuscript, the article processing charges would be waived.  I received no immediate reply.  On March 27th, however, my reply arrived after I asked the journal a second time about this issue.

I would like to inform you that our group is an open access journal group which is running on the gracious contribution of authors. Since we have invited you for the submission, we can provide you with the maximum discount on the publication fee.

We are confident that you will always be there to support us.

By now the journal was more confident that I would always be there than I was!  My reply was terse:

When you say “maximum discount,” do you mean “no page charges?” Any fee for publication will not be acceptable to us.

Their next message contained the kicker. The “maximum discount” would equal $719 (USD).  The journal office noted that their standing as an open access journal required these fees to continue operation.  After a quick discussion with another professor who had joined the writing team, I replied that no manuscript from us would be forthcoming.  At base, I know that the ideas forming in my research group are good enough that we can get them published in a journal that doesn’t have a publication fee.  I recall that some of the journals I read regularly mark paid-for papers as “advertisements” rather than as research.

March 28 Aftermath

Was it all a misunderstanding?  Was the journal intending to bring up the fees only after my manuscript was already in their hands?  Am I just as unreasonable about paying for publication as I am about paying for parking my car?  I don’t really know.  I think it’s worth assessing the effects of this incident:

  • This was not wasted effort.  We assembled a team of four to produce this manuscript, and our two trainees received the message that what they are working on is not just a cul-de-sac but rather something novel that the investigators want people to see in a proper paper.
  • If we could publish this little nubbin, we could publish a thorough investigation.  We are distilling out the key points we want to make about quality control, and we are organizing the data sets that we will need to tell it in a more representative way.
  • Dance with the ones that brought you.  My publishing career spans eighteen years.  I know exactly what to expect when I submit a manuscript to the key journals of my field, and I can trust that the review will be fair (not always positive, but fair).    When I move to new publishers, I am going to encounter knocks as I ram into barriers to which I am unaccustomed.

Given the extended conversation my field is not having about predatory publishers and the high prices of access to academic research, each professor should ask him or herself what we prioritize in communicating our work.  I sometimes come across as a bit of an old-schooler on the topic of publication; I see it as the primary deliverable of being an academic.  This brouhaha with OMICs International may demonstrate that I have bounds on “publish or perish.”  I do not believe that any price is worth paying just because it results in a published paper.

Zanzibar: the Victoria Garden Museums

An index to this series appears at the first post.

Our last full day on Zanzibar gave us a chance to visit a pair of museums grouped around the Victoria Garden.  They don’t get much attention in the guide books, but we enjoyed our look at the Zanzibar Museum of Art and the Natural History Museum.  Just what would we find beyond the archway at the southern traffic circle of Stone Town?

Rather than scurrying about as our time on the island drew to a halt, Natasha and I relaxed with a bit of light shopping during the morning.  We began with a couple of women’s collective arts stores in the Hurumzi district at first.  We liked some appliqué pillows, though they were priced a bit higher than we thought appropriate.  We saw some shirts and shorts that might look nice for me, but again their prices were high (going to $30 USD for shorts seems excessive to a frugal mind).  We enjoyed a couple of antique shops.  At one, Natasha found a box with pivoting lid intended for salt and pepper; she acquired that for holding earrings.

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A coin minted in India features a British monarch but is used off the cost of Africa…

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The High Court of Zanzibar

At another, I spotted an Imperial British coin from India featuring Queen Victoria. I think my brother might use that with his students to show that Africa and India were actively trading with the rest of the world around the time of the American Civil War.  I also found a Quran in Arabic that I wanted for my brother’s classroom.  We returned to a T-shirt shop near our jetty from last night to purchase some T-shirts for little ones in the family.  It was a good run!

From there, we took the road south past the High Court and State buildings (photos of government buildings are not permitted, though I snapped the High Court without realizing what it is).  The way ahead was blocked, so we headed away from the coast, and happily that course led next to the Victoria Gardens. This park, also called the People’s Gardens, was dedicated to the people of Zanzibar by Sultan Hamoud in 1899 to celebrate Queen Victoria’s Diamond Jubilee.  A 1996 renovation has produced a park that still looks a bit ragged, but some of the trees there are still rather pretty.  A large house adjoining the garden that was originally constructed as the British Residency now serves as the State House: the official residence of the Zanzibari president.

Zanzibar Museum of Art

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The Peace Memorial now houses the art museum.

The park adjoins a complex of two museums that we both enjoyed.  For 6000 Tanzanian shillings ($2.70 USD), we gained access to both the Peace Memorial Museum (now the Zanzibar Museum of Art) and the Natural History Museum.  The Peace Memorial building dates from 1920 during the reign of George V.  It was constructed in honor of those who lost their lives in the “Great War,” commemorating the “victorious peace.”  Why would Zanzibar have cared who “won” World War I?  As it turns out, the British used the island as a repair base for its navy.  The “Battle of Zanzibar” saw the German cruiser Königsberg sink the British cruiser Pegasus during 1914.  The Peace Memorial building looks quite unlike other World War I memorials that I have seen, such as the Liberty Memorial in Kansas City.  One might easily mistake it for a mosque, with its high dome surrounded by six smaller domes!

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The minaret of the Mnara Mosque may date to the seventeenth century.

As I mentioned, the building now houses an art museum.  Visitors are not going to see long galleries full of oils flanked by a massive sculpture garden, though.  I would highlight a few items as worth seeing.  The first is a set of miniatures.  Since Stone Town has dilapidated quite a bit, it can be hard to imagine this city in its prime.  The minaret for the Malindi / Mnara Mosque, is one of the oldest structures standing in Stone Town, though it is now matched to a mosque below that was constructed in 1834/5 (Sheriff pg.51).  It now abuts buildings on almost all sides, so the miniature version at the museum is the only way to see the mosque as a separate structure.  “Zanzibari mosques are very plain and unobtrusive, hardly distinguishable from domestic buildings.  They normally form a continuous line with neighbouring domestic houses…” (Sheriff pg. 5)

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The Old Dispensary (1899) incorporates a strong Indian influence.

The Old Dispensary is a major landmark in Stone Town.  Its story revolves around a fabulously wealthy Ismaili businessman of the late 19th century named Tharia Topan.  As one measure of his wealth, a tract of land he owned in the Ng’ambo (the other side of Creek Road) was so large that it contained 1300 huts (Andriananjanirana-Ruphin pg. 101).  When he decided to create a hospital to celebrate Queen Victoria’s Golden Jubilee, he spared no expense.  He chose a plot of land that would be prominent on the coast (though the extension of the port later blocked its view), and he brought architects and craftsmen from Bombay to create a building better suited as a palace than as a hospital.  The building uses teak imported from India throughout its structure.  He crafted a golden trowel for the ceremony of laying the building’s foundation stone and shipped it to London for exhibition.  Unsurprisingly, he was knighted in 1890, but a year later he was dead.  He never got to see the completion of his triumphant creation (Battle pg. 91-99).

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This evocative statue is displayed without details.

Next, the museum gives a corner chamber to the topic of ceramics, mostly a set of pots and vases.  On a shelf, though, stands a small statue of a chained female slave, looking down but not defeated.  I was really moved by the work, especially since our visit to the Slave Market Museum had reinforced the importance of female slaves in the role of “concubine” or “second wife.”  Many of these women decided against accepting freedom since it would mean separation from their children and other violations of dignity.  I had noted that the Slave Market Museum relied heavily on photographs and text; incorporating this statue could add depth to their presentation.  As it stands, the statue is presented without annotation of sculptor, date, or even title.

Natasha called my attention to Mr. Naaman‘s brilliant recreation of an 1840 photograph by Gillian depicting Stone Town from above.  What makes it brilliant?  The artist made it entirely by pasting together fragments of different banana leaves in 2005, using different species to achieve different shadings.

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Stone Town, executed in banana leaves

Everywhere Natasha and I have gone in Zanzibar, we have been greeted with Jambo (“Hello”), Karibu (“You are welcome”), or Hakuna Matata (“No worries”).  I learned another phrase from a museum piece showing a woven fish trap.  It reads “kuingia demani,” which means getting into problems that one doesn’t know how to solve.  I think we can all relate to that!

Natural History Museum

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Natural History doesn’t get a dome.

Visitors to the Art Museum are also encouraged to visit the small natural history museum next door.  We were both worried that the chamber would be filled with dusty Victorian taxidermy animals. While some stuffed animals were indeed present, we encountered a few things that kept our attention.  For me, the first was a partial skeleton in a glass box locked in a wire cage on the wall.  The description indicated that the skeleton represented the bones of a dodo bird from Mauritius (a gift of W. Harold Ingrams, Esq.).  This might not seem so remarkable, but remember that the last accepted dodo sighting took place in 1662!  These bones are either fakes, or they are more than three and a half centuries old.

We puzzled over a really large vertebra standing on a small table. It must have been a foot across on the central column.  At first we thought it might be from an elephant when Natasha snapped her fingers and realized it was from a whale.  My attention was also grabbed by the jaws of a largetooth sawfish (Pristis microdon) and a common sawfish (Pristis pristis).  They look something like a chainsaw blade with inch-long teeth sticking out on either side. Outside the building, Natasha noticed that the museum was once home to giant tortoises.  Gladly, the animals have been moved to nearby “Prison Island,” where we hope they have more room to maneuver.

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Sawfish teeth

Abyssinian Maritim Restaurant

For dinner, Natasha and I decided to break from Tanzanian food (which we like) to enjoy an Ethiopian restaurant we had spotted near the SW corner of Stone Town.  The restaurant had large posters of sites in the country to tell some of the nation’s history.  Because we started accumulating insect bites the moment we sat down, we decided to move to a more internal table; sadly, the insect bites continued.  We realized from the menu that our dinner was going to cost substantially more than we had been spending.  A normal lunch at a local food joint might cost 12 or 13,000 shillings.  We opted for a vegetarian entrée for me and a chicken entrée for Natasha, and we added a bottle of water and a spiced Ethiopian tea on top.  The total bill came to 49,000 shillings ($22 USD), so ultimately it was “much of a muchness.”

We wandered north toward the tourist area when Lady Hellen appeared at her shop door.  Where had we been?  Didn’t we know she was waiting for us?  Laughing, we stepped inside.  Natasha found two refrigerator magnets, and I bargained for a watercolor of a Zanzibar door that would form a nice triptych with our dhow and street paintings.  She seemed nonplussed at the small purchase, but she still showed good grace.

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Our three watercolors: town, dhow, door

Our efforts to get back to our hotel produced an unusual result.  I headed for the southeast corner of the Old Arab Fort, and then I marched us into the maze of alleys.  The Friday evening crowd on the streets had collectively decided to close up the shops.  Somehow I got us entirely turned around, and we popped back out near Freddie Mercury’s house!  This time Natasha took the fore, and she charged us back into the maze.  Once again, we took a wrong turn, and we bounced out of the maze near Lady Hellen’s art shop!  We decided to play it safe with our last effort.  We headed south and east along the belt road, and then we walked northeast along a familiar track back to our New Mkunazini Road, bought one last bottle of water, and then collapsed into our room at last!

The birth of a new conference

An index to this series is found on its first post.

November 1, 2017

How does a new conference enter the academic calendar? I was encouraged by the example set by the Clinical Proteomics / Post-Genome Medicine meeting (ClinProt 2017), and I thought it might be useful to talk about some of the things that the group did really well, while relating a bit of what unfolded for me in my last day at the conference.

Logo_BGRS-shrinkFirst off, this is far from the first meeting to take place in Russia on the subject of human proteomics. The Russian Human Proteome Organization has been operating since 2002, and it sponsors two distinct meetings yearly. The main meeting takes place in the city of Kazan each October. Members who are particularly interested in bioinformatics may participate in an annual meeting at the city of Novosibirsk (Bioinformatics of Genome Regulation and Structure / Systems Biology). The RHUPO has also successfully organized a big event for the world HUPO; in 2009, Dr. Alexander Archakov hosted the third Human Proteome Project Workshop in Moscow!

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Human Proteome Project, Moscow (2009)

The ClinProt 2017 meeting seemed special in that it sought to foster connections among many different institutions within Russia; the program was salted with several investigators across Europe and the broader world, but the emphasis seemed to be on developing networks within the country, including multidisciplinary links. As I look across the eleven-member organizational team in the conference program, I see five different research institutions, all in Russia, represented by post-doctoral scientists. This team of junior researchers will all have valuable experience for the future, and senior scientists who attended the meetings will remember who they could rely upon when trying to solve a last-minute problem before a talk!

I would catalog several things, then, that the organizers did right:

Skin in the game
Because several institutions contributed organizers, more schools sent speakers, poster presenters, and trainees. In total, 350 people registered, and 274 attended. That’s pretty great for a first conference!
Personal touch
Several speakers mentioned that they had been recruited by an organizer who knew them from prior contact. Since professors frequently get spammed by for-profit conferences, these personal contacts made a difference in getting the names they wanted for the meeting agenda.
Detail focus
I heard several of the organizers quietly worrying about whether something was going to go just right. Throughout, it was clear that each person knew what his or her responsibility included. The team was definitely committed.
Industry works
I occasionally hear academics sneer at the inclusion of instrument and reagent vendors in speaker rosters, but their participation in a meeting adds more than just money. I was glad to see a representative from Helicon lecture on the value of CyTOF for cell counting applications, since I am mentoring a student working with such data.

I became aware that we had some special guests today as I lingered in the speaker ready room. Several people in suits made an appearance. I had a rapid conversation with Sergey Suchkov, an M.D. and Ph.D. who has a relentless energy about him. He has a strong interest in developing relationships among BRICS nations in the field of “precision medicine” (sometimes called “personalized medicine”), and he wanted to talk about some possibilities between South Africa and Russia in that space. We agreed to touch base this afternoon when he could introduce me to another M.D. Ph.D. friend of his who has become involved in genome bioinformatics. That meting put forward some interesting possibilities in tuberculosis, which has become problematic in the Russian prison system. I hope we will be able to define some projects we can pursue together in this space.

Right away, though, I had to leave our discussion to teach my afternoon workshop on performing post-hoc quality control assessment in large-scale proteome projects. I was very grateful that the conference organizers could add a link to their website so that participants could download the R statistical script and input files for the workshop directly from the link above. That way the conference attendees who needed to leave Moscow early can still get access to the tutorial.

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Image from my paper with Xia Wang introducing “IDFree” metrics

This was my first time to teach a workshop on quality control. My normal curriculum has emphasized protein identification or the recognition of post-translational modifications. Since I am now chairing the HUPO-PSI working group on quality control, though, it was a good time for me to put together some training materials in this space. I chose a highly visible data set, the 1425 LC-MS/MS experiments that the Vanderbilt team produced from colorectal cancer samples for the National Cancer Institute CPTAC program. The workshop would focus on recreating figures that Xia Wang at U-Cincinnati had scripted in the R statistical environment from tables of QC metrics that my team had generated.

I was really pleased with the dozen or so students who attended the workshop. Their questions were very good, and their understanding of the statistical concepts was at a very high level. To give one example, a student asked how differently the files would have spread in my plot of the first two principal components if we had used ordinary PCA rather than robust PCA. Another asked how hierarchical clustering would visualize these data in principal components space. These are not the questions one encounters with people who have never seen PCA before!

So color me impressed. This meeting ran like clockwork, and the students came ready to learn. The speaker list did not have some of the biggest names in world proteomics, but in fact I trusted what I was hearing more because it came from investigators who had worked at the bench more recently. I am of course grateful for the time I’ve been given to see Russia first-hand, but in the end I was brought here to teach and to learn. I enjoyed both missions!

 

Clinical proteomics in Russia and my last pair of pants

An index to this series is found on its first post.

October 30, 2017

At last the first day of ClinProt 2017 had arrived! I set aside my now-muddy pairs of jeans in favor of my fresh and clean blue dress pants, laced up my shiny black shoes, and put on my enthusiastic green shirt. With a spot of breakfast downstairs (on my third morning eating there, I found that the milk jug was full for the first time!), I was ready to meet with the others for a shuttle van ride over to the conference.

Moscow traffic at 8:20 AM is a bit intense. The drivers here are a bit more careful of road laws than I have seen in other countries, but they still produce some pretty creative merges in their traffic jams. What would have been a few minutes on the subway was more like a half hour on the road, but my dress pants were still pristine when we arrived at the Congress Center at the I.M. Sechenov First Moscow State Medical University. The facility had a lovely central hall, with a graceful split staircase to the two main venues for our meeting. I hadn’t seen lecture halls in which an array of nine HDTVs replaced the more typical projector. It certainly produced a bright image, though the borders between screens were distracting.

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Why project when you can emit?

The Clinical Proteomics 2017 meeting was organized because a confluence of groups wanted to consolidate researchers in this country. EuPA, the European Proteomics Association, helps to integrate activities that span national proteomics societies. The Russian Human Proteomics Organization (RHUPO) sought to foster a sense of community among Russian research groups in this area. The Sechenov First Moscow State Medical University was happy to contribute a venue for the event, and many instrument, reagent, and other vendors agreed to take part, as well. I haven’t learned the total count of attendees yet, but I know that there are 87 research posters. For a first effort, I think it is clear that a great many things have gone well.

From the very first talk, it was apparent that Russian clinical proteomics researchers are grappling with challenges that became familiar to me as part of the National Cancer Institute (NCI) CPTAC program. Anna Kudryavtseva discussed her efforts to reconcile proteomics data with those that had been produced by NCI The Cancer Genome Atlas (TCGA), working in a particular sub-type of head and neck cancer. Prioritizing genes that were more frequent targets of mutation in tumors has value for understanding which proteins are most useful to monitor closely, for example. It was a great “plenary” (all attendees) talk to kick off these discussions.

As soon as we split to multiple sessions, I was on duty. I co-chaired the “Genomics and Beyond” panel with Sergey Moshkovskii. It was a bit odd to be fielding this panel while the Protein Informatics workshop was taking place in another room (that topic has been my bread and butter for two decades)! In this case, however, Sergey and I were not only chairing the session but also leading it with our two lectures, both in the field of proteogenomics.

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Photo credit: Olga Kiseleva

I defined the term by saying that we want to improve our interpretation of genomic data by integrating proteomics data, and we want to improve our interpretation of proteomics data by integrating genomic data (I was trying to be ecumenical). From there, I led the group through the new paper that I’ve published with Anzaan Dippenaar and Tiaan Heunis, in which we demonstrated our ability to recognize sequence variations and novel genes in Mycobacterium tuberculosis “bugs” that had been isolated from patient sputum in South Africa. Sergey followed up by finding evidence of RNA editing in fruit flies.

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Photo credit: Olga Kiseleva

The other speakers in the panel were also quite interesting. Matthias Schwab was visiting from Germany, and he educated the group on the current status of the field of pharmacogenomics. Vladimir Strelnikov, a geneticist, described the value of bisulfite sequencing for measuring DNA methylation in breast cancer. Sergey Radko outlined a SISCAPA-like strategy for using “aptamers” to enrich proteins prior to Selected Reaction Monitoring. Artem Muravev closed out the session to discuss the challenges of biobanking. This last talk was delivered in Russian, so I benefited quite a lot from real-time translation to English by Anastasia, one of two translators fielding our session (during my talk, she had been translating my words to Russian as I worked through my slides). Finally all the speakers came together for fifteen minutes of question and answer. I tweaked our pharmacogenomics speaker a little bit by saying that even if we had the complete sequences for every human on earth in our hands today, personalized medicine would not have arrived!

With the morning complete, everyone adjourned to a nearby restaurant. I was a little leery when I learned our destination was the Black Market, but I needn’t have worried; we wandered down the street to a lovely restaurant named “Black Market.” I had the Black Market Burger and felt thoroughly happy. I felt very grateful that the European Proteomics Association picked up the bill for that morning’s speakers!

Back in the conference, I enjoyed hearing my long-time friend David Goodlett discuss his long-term monitoring study of diabetes. He’s a careful guy, and it is good to see that he can make label-free proteomics sing in biofluids (a tough space to work), recognizing protein pairs for which expression can flag the onset of disease. It’s very reminiscent of the kind of study Stellenbosch University has produced in the space of tuberculosis. Our next speaker returned to the subject of biobanking, and he delivered his talk via Skype, not my favorite format. I am a big believer in contact with my audience.

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Did I mention it was my enthusiastic green shirt?

I threw all my remaining energy into the poster session. Interacting with researchers at the start of their careers is very rewarding, and people who stand beside their work without knowing whether or not anyone will take interest have a hard job. These students were even braver, since they were prepared to defend their work in English!

I started with a poster very near and dear to my heart. A.V. Mikurova was evaluating the different levels of sequence coverage achieved by database search (Mascot, X!Tandem) and de novo algorithms (PepNovo+, Novor, and PEAKS) when working with 27 LC-MS/MS experiments for a defined mixture of human proteins. We discussed the relative unresponsiveness of sequence coverage as a metric for performance evaluation and the challenge of ensuring the algorithms had comparable configuration. I asked S.E. Novikova about her choices of statistical model for a time-series measurement of proteomes in response to all-trans retinoic acid. I hope my statistics lectures online will be useful to her, though it sounds like she’s already on the right track. N.V. Kuznetsova taught me a few things I didn’t know about celiac disease! She had been evaluating the ability of Triticain-Α to degrade the most immunogenic peptide of gluten-family proteins. Finally, J. Bespyatykh was presenting a poster on the proteomics of Mycobacterium tuberculosis from a strain called Beijing B0/W148. Her work obviously had a strong relationship to what Tiaan and Anzaan had published with me, so we had a great conversation about the work. I hope we can help her find a sequence database that is a more ideal fit for her proteomes than the generic “H37Rv” protein database. I was really pleased to speak with so many students about their work at this meeting.

With that, I slumped onto a wall and didn’t move very much. The other conference attendees had flowed back into the conference room for an afternoon round of talks. I let my mind wander for a bit, though I did have some nice conversations with the vendors. Soon, though, I heard some odd noises echoing through the entry hallway. Was there a music practice room somewhere in the building? Was that a tuba?

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Dixieland music in Moscow! Photo credit: Olga Kiseleva

My questions were answered when I eventually joined everyone downstairs for a catered closing reception. The organizers had invited a Dixieland band to perform for our reception! The group was really solid. I particularly liked one of their trumpeters, since he had a smooth Chuck Mangione vibe going on. I kept recognizing songs only part of the way, since they were singing many of the lyrics in Russian! I finally got a solid hit on “Mack the Knife!” I sat up close to enjoy the show.

With the evening at an end, I declined invitations to go hit a bar and walked to the nearby Frunzenskaya subway station. Two stops later, I was in my neighborhood. I trudged up the paved driveway to the street with my hotel. As I awaited the green light at my last crosswalk before the hotel entrance, a car drove too close to the curb where I was waiting, and dirty rainwater soaked my last clean pair of pants.

 

You can be an academic YouTube STAR!

Many universities have begun exploring the use of the Internet for sharing academic coursework, either via “flipped classrooms” or Massive Open On-Line Courses (MOOCs).  Over the last year, I have uploaded approximately 50 videos to my YouTube Channel, most of them academic lectures.  I hope that I have learned something in this process that will you to publish your work more broadly, as well!

I would start by explaining that my lectures come from multiple purposes and even multiple university campuses.  My longest-running series of lectures came from a weekly seminar on topics of my own choosing called “the Useful Hour.”  I produced fourteen of these sessions (with help from Brigitte Glanzmann when I had to be away for a week), though I only started recording them on video for the last twelve.  I recorded the eight-session bioinformatics module from our division’s B.Sc. Honours program as a trial run for creating a “flipped classroom” in future years (a model where students watch lectures outside of class and spend in-class time working exercises).  More recently, I collaborated with the H3Africa BioNet to produce a four-lecture module on Gene Expression.  From time to time, I help the Tygerberg Postgraduate Student Council by recording a lecturer.  Each of these experiences has had its own lessons to convey.

The technical aspects of recording a video are generally easy enough that even a Ph.D. can do it!  Today’s budget camcorders capture more detail with better sound under lousier conditions than did cameras that cost five times as much even five years ago.  Best of all, one no longer needs to wrestle with tapes and analog-to-digital transfer loss.  Today we simply pull the Secure Digital card out of the camcorder and plug it into the socket on a laptop, where the video files are instantly accessible.  Of course, many people record video using digital cameras or cell phones.  Preparing videos for upload to a public server, however, is frequently more difficult than the initial capture.  I’ll talk about these aspects below.

Focus on the speaker

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Speak softly, and carry a big stick!

We must start with video that is worth watching.  Far too frequently, I see that people recording lectures focus on the slides rather than the person who is delivering the lecture.  Reading text from video is generally unpleasant, and the reality is that looking at people fires circuits in our brains that academic content does not.  Video is a format designed to capture motion; it is a notoriously inefficient method for capturing still images, though!  Keeping the camera on the speaker, then, makes more sense.  This comes with some caveats:

  1. Viewers still need to be able to see the slides.  My answer has been to produce a PDF from the PowerPoint or other presentation software, since almost everyone has the ability to view PDFs on any platform.  I post the PDF to a shared directory on Google Drive, and I include the URL leading to the PDF in the YouTube description.
  2. From time to time a researcher will point to a particular part of a slide.  This is probably problematic on video; if he or she has used a laser pointer, the spot of light will either be too bright (green) or too dim (red) to appear well on video.  A moving mouse pointer might be better.  If the speaker is old-school (like me), he or she may use a stick to point at the slide instead.  This can create a problem of the lecturer “blooming” as he or she moves away from the bright field created by the projector into the relative dark outside the projector’s light.
  3. How will a person watching the video know to advance to the next slide?  Hopefully the speaker says “next slide” out loud.  When my parents recorded my brother’s and my first efforts to read aloud, they told us to bang a spoon against a mug to produce an audible chime with each page turn.  That was even more fun than reading!
  4. Software is publicly available to integrate the slowly-changing slide video with the quickly-moving speaker video.  Screencast-O-Matic will produce videos of up to fifteen minutes in its free version.  This approach will guarantee that your viewers are seeing the same slide the lecturer is seeing as the talk progresses.
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Screencast-O-Matic insets your image atop the slides you are presenting.

Light and detail go hand in hand

As I alluded above, lighting is frequently a problem in academic lecture videos.  We frequently keep our lecture halls very dim in order to make the slides stand out as much as possible.  In a large venue, you may have a spotlight on the speaker, which will help.  In a medium venue, you may have a light in the ceiling directly above the speaker, which can make him or her appear somewhat ghoulish.  The more you rely upon zoom, the less light will reach your camera!  Keep that camera close.  If you can open the blinds on a window so that your speaker is lit, you will have a more interesting video.  Try to find ways to position your camera between the light and the subject (without casting a shadow, of course).  Never forget that the projected slides are much brighter than the subject you are trying to record.  If even the corner of the projected image appears in-shot, expect the speaker to become a flat silhouette.

Today’s cameras can record in very high resolutions, such as 1080p (the same as your HD television).  If lighting is truly problematic, you may want to consider forcing your high-resolution camera to a lower resolution, such as 720p; this may allow it to combine intensities across multiple transistors for each pixel.  Similarly, you should expect that a camera with a larger “retina” will outperform one with a tiny CCD in low light.  To put this in plain terms, do not expect a cell phone to produce quality video in semi-darkness, no matter the name on the label.  That said, I have observed that my “mirrorless” Canon EOS-M2 is inferior to my much cheaper Canon VIXIA HF R62 for video.  The lenses and electronics of the EOS-M2 are optimized for photos, not video.

Privacy issues are a big deal

Ensure that your audience knows that the lecture is being recorded.  Bad things can happen when a person does not want his or her image to be on-line and somebody else decides that they shall be.  Imagine how much worse this becomes when that member of the audience is a minor!  Nobody should be forced into public view because he or she attends a talk.

We frequently expect a period of questions and answers at the end of a lecture (and sometimes in the middle).  A novice camera operator may automatically swing to capture the questioner in action.  Depending on the situation, this part of the video may need to be truncated outright due to privacy issues.

Video is big and hard to handle well

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I use my hands a lot.

When I upgraded to my Canon VIXIA HF R62 from a JVC Everio (GZ-HM30AU), I had a rude shock.  My old camera had captured 720p video in very manageable MTS files, but the new camera captured 1080p video in massive MP4 volumes.  I used a 16 GB SDHC card for videos.  The cameras assumed that no file should be allowed to be larger than 4 GB (linked to 32-bit computing).  With the new camera, I consume 4 GB every 33 minutes!  At a couple of long events I recorded, I found that I needed more storage than the 16 GB card could provide.  I solved that problem by upgrading to a 64 GB card.

Naturally, keeping the raw footage of every event I video is not practical.  If each of the 50 videos I posted to YouTube over the last year produced 66 minutes of raw footage, I would need to archive 400 GB for just this period!  Similarly, posting these videos to YouTube would be a problem.  Each hour would span two files, which would require my viewers to watch part ‘A’ and then queue up part ‘B’ immediately afterwards; many would just skip watching the end, humans being humans.  To compound the problem, I live in South Africa, which means my upload speeds to network servers are dreadfully slow.  My home DSL line, for example, achieves 0.3 Mbps.  I have uploaded one GB before, but it takes hours.  In any case, I will probably need to truncate a bit of time off the front and the back of the video.  In short, I need to do video editing.

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While semi-professionals might opt for Adobe Premiere and those who “think different” will break out iMovie, I am a bioinformaticist, and I like software that lets me master high-quality videos with a minimum of fuss and bother.  I use ffmpeg, a very powerful suite of tools that one can use directly on the command line.  Most of the time, I am (a) concatenating my source video files into one movie, (b) including only a middle section, and (c) writing a more compact movie from the source materials.  To use a recent example, I have two input files; I write their names into a file called list.txt:

file mvi_0031.mp4
file mvi_0032.mp4

Next, I run a command line that looks like this:

ffmpeg.exe -ss 00:00:15 -f concat -safe 0 -i list.txt -t 00:50:00 -c:v libx264 -preset slow -c:a copy output.mp4

In order, the options do the following:

  • -ss specifies where in the combined files ffmpeg will start the output video (in this example, after the first fifteen seconds).
  • -ff concat -safe 0 -i list.txt specifies that the files listed in list.txt should be combined into one video and that they are formatted the same way.
  • -t specifies the total duration of the video to be encoded (in this example, exactly fifty minutes).
  • -c:v libx264 -preset slow specifies that my output video will be MPEG 4 pt 10, a very common format for storing video (and one that YouTube knows how to read).
  • -c:a copy directs ffmpeg not to re-compress the audio, making it sound just as nice in the output as it did in the original.

The ffmpeg software is very good at reducing the size of videos without compromising its quality.  I find that I can represent an hour-long lecture in a two GB 1080p video, rather than the nearly 8 GB of source footage.  If I am filled with caffeine for my lecture, the video size increases a bit (more motion requires more bits for accurate representation).

These smaller videos can then be uploaded to my YouTube account.  Happily, if you have a Gmail account (or if you use a different email address to log into Google Services), you can simply use that login for YouTube.  One clicks the arrow pointing up, and a screen will appear to which you drag your video file.  All done, right?

No job is finished until the paperwork is through!

Meta-data is key to your video reaching an audience, and too few people spend adequate time on this step.  I would call your attention to both the “Basic Info” and “Advanced Settings” pages that video authors can complete.  Of course, you should enter a paragraph of information in the basic description blank.  Ask yourself what web searches should find your video, and be sure you include those key terms in the text.  For good measure, add them again in the keywords section!  I like to include the university name where the recording took place.  Hopefully the social media minders for these schools will highlight your video to their large audiences.  YouTube will sniff the video for still frames that might be representative for the video.  I always try to pick the one in which I do not look like I’m suffering a fit of some sort.

Advanced Settings has more options to help users find your video.  Pick a category; generally my lectures fall in the “Science and Technology” category.  Be sure to enter a video location.  Google will translate your information to GPS coordinates so people can find videos shot near particular locations.  Enter a recording date, and select the language of your video (especially if you are not using English).

In many cases, you will have several videos that belong together as a set.  When I produced a short biography and four videos on Gene Expression for H3A BioNet, I also created a “playlist” that contained all five videos in the correct order.  Remember, if you can hook a viewer into watching one of your videos, you might be able to retain their interest for a few more!  Ideally, people will like your stuff enough that they subscribe to your YouTube channel, receiving a notification every time you post a new video.  You will be launched on your next career as a YouTube star!