PF11 SNP geographic analysis suggests that the Ukraine cases in the next two weeks may show a very similar genetic pattern to South America in August and the Mediterranean and Adriatic FlightPath in the past 8 weeks.
If the trend toward a higher infectivity of medical personnel continues as reported today of 687 doctors and 1,500 young specialists being ill, we would expect a higher death count in the coming days. Between 0.5% and 1.3% of all doctors in the country are ill (by region). Higher transmissibility is certain.
If a database of 100 sequences were to exist on the Ukraine, accurately cataloging a cross-reference of regions over 14 days of recent death and recovery cases, including major cities, rough expectations would indicate:
HA
225E
in moderate concentration (95% probability) with 206T
206T/225E/300S triplet
potential for introduction (1 sequence) (75% probability)
2E/206T/225E/298V quad combo
potential for appearance in very low count (1 to 2 sequences) (>25% probability)
2E/206T/225G/298V quad combo
potential for introduction (1 sequence) (<10% probability)
225G
potential, but certainly not widespread under current clinical reports (75% probability) with 206T
2E/206S/296H triplet
in low concentration (95% probability)
377K
potential for introduction (1 sequence) (25% probability)
270T
potential for introduction (1 sequence) (7% probability)
261V
potential for appearance in very low count (1 to 3 sequences) (>25% probability)
212 movement
potential for introduction (1 sequence) (7% probability)
208K
potential for introduction (1 sequence) (33% probability)
188/189/190 movement
potential for introduction (1 sequence) (>50% probability)
158E
potential for appearance in very low count (1 to 3 sequences) (>25% probability)
100N
potential for introduction (1 sequence) (>25% probability)
35I
potential for appearance in moderate count (<20% probability)
NA
106I, 248N pairing
potential in very low count (<20% probability)
106I, 248N, 286G triplet
potential for introduction (7% probability until the 8th week of the flashfire)
Showing posts with label 248N. Show all posts
Showing posts with label 248N. Show all posts
2009-11-09
2009-10-23
Potential Catalyst for Pandemic 2.0 Emerges in Italy during July
During the Summer of 2009, an unsuspecting twelve year old boy in Veneto, Italy may have become the host of an influenza strain that is now setting the Pandemic 2.0 stage.
The Northern Italian region of Veneto has a population nearing 5 million and hosts 60 million tourists each year with many passing through the canals of the capital, Venice. The Laguna Veneta is the largest wetland in the Mediterrean (340mi2 / 550km2) and the delta serves a wide range of migratory bird species.
The University of Padova lab deposited 24 Neuraminidase (N1) sequences today from Italy sampled during July 2009 (Pandemic 1.5) bringing the total number of Italian NA segments on file to 26. Antigenic diversity is observed in the Italian sequences, several with novel introductions, but the point variations are not our primary interest in this very important deposit.
One sequence from the Padova lab signals the first recorded instance of a key transition for this pandemic. The NA Triple Combination may mark an axis or inflection point for PF11. A/Italy/134, from a student (12M) in Veneto, demonstrates a match to Seasonal Influenza in a permutation of 3 key markers that we have anticipated as a potential catalyst to Pandemic 2.0.
A Balkan emergence had generated the highest probability in our research with the Italian peninsula and bounding northern states ranking as "Very Probable". Few sequences have been made available to evaluate the Balkan states during this pandemic, so we cannot determine if the recombinations occurred in that area as well as in Italy. Emergence was expected within a 250 mile radius (400km) of a significant body of water, particularly the Adriatic Sea, the Black Sea or the western boundary of the Caspian Sea. Of course, we may be searching for our keys under the streetlamp. So little surveillance is surfaced at this point that rough estimates are the maximum any lab may produce.
In Italy134, this coalescing set of 3 human-fit markers, predicted by our research in mid-May, emerged during the summer, recombined as expected onto the swine N1 background. As you may observe from the positional study, this sequence may have required two or more in situ polymorphisms from consensus within this geography to gain these genetics. In the estimation of our research team, random mutation is a less than stellar explanation. Human-fit Seasonal Influenza and ΣPF11 now have much more in common as ΣPF11 moves into tighter conformation potentially gaining trait enhancements.
Neuraminidase Triple Combination
106I, 248N, 286G : Italy134
106I, 248N, 286G : Seasonal Influenza 2005, 2006, 2007, 2008, 2009
106I, 248N, 286G : H5N1 (Avian, Human), H1N1 (Avian, Swine)
106I, 248N, 286G : 1918 Brevig Mission
This July sequence lays additional groundwork for attractant donations from candidates in previously observed donor serotypes.
Few Italian points of comparison are available prior to this large NA deposit. Of the two, NA Italy05 is unremarkable for this study and NA Italy127 is quite remarkable due to temporal and geographic proximity, as you will see in the Italian permutation discussion. We also note that the Hemagglutinin segments so prolifically available from Italy demonstrate exceptional variance (20 major polymorphisms from 34 Sequences). These Hemagglutinin amino acid revisions include, but are not limited to, 137T, 199N, 200T, 219T, 225E (4), 244I, 261G (2), 277E, 296H (4) and 300S (2). NA variance is correlated with HA variance in ΣPF11.
Antigenic Diversity, even within the sparse 26 Italian NA sequences is observable if only upon reviewing the four permutations of the Neuraminidase Triple Combination.
106I, 248N, 286G : Italy134 from Veneto, sampled 2009-07
106I, 248N, 286S : Italy127 from Veneto, sampled 2009-06-17, 256L (H3N2, H5N1 Avian)
106I, 248D, 286S : 23 Sequences, including Italy05 from May 2009
106V, 248N, 286S : Italy149
Italy134 is most similar at the protein (468/469) and nucleotide (1407/1410) levels to two different groups of sequences: the NA 286G bearing group from Canada (5 of 6 Sequences) and the Asian group (with Louisiana03) carrying the rare PF11 dual combination of 106I and 248N (20 sequences). The Russian Almati01 and Ekaterinburg01 round out the set with the 106I/248N pairing, but vary at an additional amino acid from Italy134. Only 24 sequences at GenBank carry the PF11 amino acid homology between 106I and 248N.
Until PF11Ω is achieved, Influenza Flux will continue to vary the virulence and transmute the transmissibility at individual geographies. Future scrutiny of the NA permutations discussed here is merited. Bear in mind that the current reservoir, even with this instance of tighter human coupling, remains hobbled by transitional genetics. Fitness determination of this Seasonal NA Triple Combination on the swine N1 background of PF11 remains to be determined at such time as sequences are surfaced.
The Northern Italian region of Veneto has a population nearing 5 million and hosts 60 million tourists each year with many passing through the canals of the capital, Venice. The Laguna Veneta is the largest wetland in the Mediterrean (340mi2 / 550km2) and the delta serves a wide range of migratory bird species.
The University of Padova lab deposited 24 Neuraminidase (N1) sequences today from Italy sampled during July 2009 (Pandemic 1.5) bringing the total number of Italian NA segments on file to 26. Antigenic diversity is observed in the Italian sequences, several with novel introductions, but the point variations are not our primary interest in this very important deposit.
One sequence from the Padova lab signals the first recorded instance of a key transition for this pandemic. The NA Triple Combination may mark an axis or inflection point for PF11. A/Italy/134, from a student (12M) in Veneto, demonstrates a match to Seasonal Influenza in a permutation of 3 key markers that we have anticipated as a potential catalyst to Pandemic 2.0.
A Balkan emergence had generated the highest probability in our research with the Italian peninsula and bounding northern states ranking as "Very Probable". Few sequences have been made available to evaluate the Balkan states during this pandemic, so we cannot determine if the recombinations occurred in that area as well as in Italy. Emergence was expected within a 250 mile radius (400km) of a significant body of water, particularly the Adriatic Sea, the Black Sea or the western boundary of the Caspian Sea. Of course, we may be searching for our keys under the streetlamp. So little surveillance is surfaced at this point that rough estimates are the maximum any lab may produce.
In Italy134, this coalescing set of 3 human-fit markers, predicted by our research in mid-May, emerged during the summer, recombined as expected onto the swine N1 background. As you may observe from the positional study, this sequence may have required two or more in situ polymorphisms from consensus within this geography to gain these genetics. In the estimation of our research team, random mutation is a less than stellar explanation. Human-fit Seasonal Influenza and ΣPF11 now have much more in common as ΣPF11 moves into tighter conformation potentially gaining trait enhancements.
Neuraminidase Triple Combination
106I, 248N, 286G : Italy134
106I, 248N, 286G : Seasonal Influenza 2005, 2006, 2007, 2008, 2009
106I, 248N, 286G : H5N1 (Avian, Human), H1N1 (Avian, Swine)
106I, 248N, 286G : 1918 Brevig Mission
This July sequence lays additional groundwork for attractant donations from candidates in previously observed donor serotypes.
Few Italian points of comparison are available prior to this large NA deposit. Of the two, NA Italy05 is unremarkable for this study and NA Italy127 is quite remarkable due to temporal and geographic proximity, as you will see in the Italian permutation discussion. We also note that the Hemagglutinin segments so prolifically available from Italy demonstrate exceptional variance (20 major polymorphisms from 34 Sequences). These Hemagglutinin amino acid revisions include, but are not limited to, 137T, 199N, 200T, 219T, 225E (4), 244I, 261G (2), 277E, 296H (4) and 300S (2). NA variance is correlated with HA variance in ΣPF11.
Antigenic Diversity, even within the sparse 26 Italian NA sequences is observable if only upon reviewing the four permutations of the Neuraminidase Triple Combination.
106I, 248N, 286G : Italy134 from Veneto, sampled 2009-07
106I, 248N, 286S : Italy127 from Veneto, sampled 2009-06-17, 256L (H3N2, H5N1 Avian)
106I, 248D, 286S : 23 Sequences, including Italy05 from May 2009
106V, 248N, 286S : Italy149
Italy134 is most similar at the protein (468/469) and nucleotide (1407/1410) levels to two different groups of sequences: the NA 286G bearing group from Canada (5 of 6 Sequences) and the Asian group (with Louisiana03) carrying the rare PF11 dual combination of 106I and 248N (20 sequences). The Russian Almati01 and Ekaterinburg01 round out the set with the 106I/248N pairing, but vary at an additional amino acid from Italy134. Only 24 sequences at GenBank carry the PF11 amino acid homology between 106I and 248N.
Until PF11Ω is achieved, Influenza Flux will continue to vary the virulence and transmute the transmissibility at individual geographies. Future scrutiny of the NA permutations discussed here is merited. Bear in mind that the current reservoir, even with this instance of tighter human coupling, remains hobbled by transitional genetics. Fitness determination of this Seasonal NA Triple Combination on the swine N1 background of PF11 remains to be determined at such time as sequences are surfaced.
2009-09-14
NA Dual Combination 106I and 248N; 22 PF11 Sequences; 1 in United States
Human-fit Seasonal H1N1 from 2008 and 2009 typically demonstrates the H275Y TamiFlu Resistance marker and a NA Triple Combination at 106, 248 and 286:
106I, 248N, 286G
As of today, GenBank shows only one sequence on file from the United States demonstrating a match to the NA Dual Combination of 106I and 248N and the consensus interior region:
Europe, North America and Asia are now penetrated with the NA Dual Combination of 106I and 248N in the PF11 reservoir matching 2008 and 2009 H1N1 Seasonal Influenza and laying the groundwork for additional TamiFlu Resistance.
106I, 248N, 286G
As of today, GenBank shows only one sequence on file from the United States demonstrating a match to the NA Dual Combination of 106I and 248N and the consensus interior region:
- A/Louisiana/03, sampled on 2009-05-01 from a 1 year old female
- Italy (1: Italy127)
- Russia (2: Ekaterinburg01 & Almati01)
- US (1: Louisiana03)
- Asia (18)
- Japan (15, including TamiFlu Resistant Osaka180)
- China (2: Shanghai71T & Nanjing1)
- Korea (1: Korea01)
Europe, North America and Asia are now penetrated with the NA Dual Combination of 106I and 248N in the PF11 reservoir matching 2008 and 2009 H1N1 Seasonal Influenza and laying the groundwork for additional TamiFlu Resistance.
2009-09-10
TamiFlu Resistance in Texas with no sample date, NA:H275Y
The NA and HA for A/Texas/47 was deposited today at GenBank with no sample date, host age or clinical notes and is a close amino acid match to the Washington28 resistant sequence.
The NA of TX47 is an exact nucleotide match at all positions (1409) but C823T (TamiFlu Resistance) with Nanjing02, Pennsylvania10, Illinois04 and Arkansas03.
TamiFlu Resistance is indicated via 275Y on the Neuraminidase. The sequence displays the following NA Quadruple Combination:
106V, 248N, 275Y, 286S
The following permutations are now represented on the eight PF11 anti-viral resistant sequences:
106V, 248N, 275Y, 286S = WA28, WA29, TX47
106I, 248N, 275Y, 286S = Osaka180
106I, 248D, 275Y, 286S = HK2369, Yamaguchi22, Denmark528, Hunan SWL3
Until the 2009-08-21 deposit of the two Washington sequences, all 275Y TamiFlu-Resistant specimens on PF11 backgrounds were paired with 106I. Today we see 3 of 8 with 106V.
The trending toward a stronger pairing of 248N with 275Y continues as discussed in the Washington Post with a 50 / 50 split of the specimens carrying Asparagine (N) and Aspartate (D).
The Hydra Effect will be more strongly documented when the population size of the sequence database increases.
An n equal to 8 gives little to contemplate.
The NA of TX47 is an exact nucleotide match at all positions (1409) but C823T (TamiFlu Resistance) with Nanjing02, Pennsylvania10, Illinois04 and Arkansas03.
TamiFlu Resistance is indicated via 275Y on the Neuraminidase. The sequence displays the following NA Quadruple Combination:
106V, 248N, 275Y, 286S
The following permutations are now represented on the eight PF11 anti-viral resistant sequences:
106V, 248N, 275Y, 286S = WA28, WA29, TX47
106I, 248N, 275Y, 286S = Osaka180
106I, 248D, 275Y, 286S = HK2369, Yamaguchi22, Denmark528, Hunan SWL3
Until the 2009-08-21 deposit of the two Washington sequences, all 275Y TamiFlu-Resistant specimens on PF11 backgrounds were paired with 106I. Today we see 3 of 8 with 106V.
The trending toward a stronger pairing of 248N with 275Y continues as discussed in the Washington Post with a 50 / 50 split of the specimens carrying Asparagine (N) and Aspartate (D).
The Hydra Effect will be more strongly documented when the population size of the sequence database increases.
An n equal to 8 gives little to contemplate.
2009-09-09
Toronto Adds 2 Sequences to NA Triple Combination Analysis with 286G
Toronto sequences filed at GenBank today add numbers 29 and 30 to ΣPF11 for 286G on Neuraminidase . The bulk of the PF11 286G sequences cluster in Catalonia, but these two sequences from Toronto augment a NA Triple Combination occurring in Canada. Canada and Catalonia are the only regions of the world currently reporting this PF11 coding that is also found in 1918 sequences, the high-CFR H5N1 Gharbiyah, Egypt specimens and is common in Seasonal Influenza from 2006, 2007 and 2008.
- A/Toronto/T5294/2009 (TorT5294) collected on 2009-05-30 from 22F
- A/Toronto/C0270/2009 (TorC0270) collected on 2009-05-24 from 33M
Human-fit Seasonal H1N1 from 2008 and 2009 typically demonstrates the H275Y TamiFlu Resistance marker and a NA Triple Combination at 106, 248 and 286:
106I, 248N, 286G
These two sequences from Toronto in May 2009 follow the worldwide pattern exhibiting a particular permutation of the NA Triple Combination:
106V, 248N, 286G
The two sequences parallel the previously discussed TorontoT5308 sequence with the exception of TorT5294 also showing 382A.
Of the 30 sequences on file bearing 286G, all but Catalonia397 bear 248N and all 30 show 106V. An intra-segment exclusivity on NA exists presently in PF11 between 106I and 286G though 106I donors are proximal in Catalonia and Canada.
Are we seeing enhanced conservation within a PF11 sub-clade being primed for TamiFlu Resistance?
106I, 248N, 286G
These two sequences from Toronto in May 2009 follow the worldwide pattern exhibiting a particular permutation of the NA Triple Combination:
106V, 248N, 286G
The two sequences parallel the previously discussed TorontoT5308 sequence with the exception of TorT5294 also showing 382A.
Of the 30 sequences on file bearing 286G, all but Catalonia397 bear 248N and all 30 show 106V. An intra-segment exclusivity on NA exists presently in PF11 between 106I and 286G though 106I donors are proximal in Catalonia and Canada.
Are we seeing enhanced conservation within a PF11 sub-clade being primed for TamiFlu Resistance?
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