So, welcome all to the CIB Virtual Computational Biology Seminar Series. Today we have the pleasure to have Georgie Krobitsch from the Laboratory of Artificial and Natural Evolution of the University of Geneva. Georgie studied computer science, he is a computer scientist during his bachelor at the Faculty of Electrical Engineering and Computing at the University of Zagreb in Croatia. He earned his master in computer science and evolutionary computation in 2011 from the same university and he joined Michel Milinkovich's group in April 2012 as a PhD student for developing meta-heuristics for phylogeny inference in the framework of the meta-pigas software. So, about the group has been 10 years that the group core activities revolve around the production of experimental data and the development of tool software and algorithm in evolutionary genetics. Since 2008 they additionally combine evolutionary and developmental biology or evo-devo and the study of physical processes to understand the mechanism generating complexity and diversity in the living world. So, the group is specializing in non-classical model species in reptiles and mammals and they integrate data and analysis from comparative genomics, molecular developmental genetics as well as computer modeling and numerical simulations. So, today Georgie will show how to explore phylogeny space with meta-pigas, the sort of software. And so, Georgie thanks again for accepting our invitation and the floor is yours. Thank you, Diana. Thanks to SIV for inviting me to speak here and thank all of you that are sharing this room with me today and you're having your attention. This is a quick overview of what am I going to talk about. I will shortly introduce the problem of phylogeny for anybody who is uninformed about it. Also the ways we reconstruct phylogenies and at the end about specifically about my project. So, what is a phylogeny problem? Actually we have entities and certain characters that are homologous so we assume that these characters have a common ancestor and we want to put them in a structure, a tree-like structure where we will try to infer which groups of entities are more closely related than other groups. In this case we have four animals and this is the character we are trying to... We are using to reconstruct their evolutionary pasts, our DNA sequences and on the right side you have a typical, very simple example of a tree that tries to explain this data and in this case we see that we grouped for example rat and pig together and cats and back together. This is just our arbitrary example. So how do we evaluate this model that explains these observed characters we have on the left? Well the simplest example, the simplest method for doing so is using parsimony method which is very straightforward and very simple to interpret. We just try to calculate the minimum amount of changes we need on such tree to explain the data. In the upper example you see that if we put the tree like so and let's say that bat and rat have some character Y and cat and pig have some character X. So in order to explain these characters in green, which is observed data, we need at least two mutations. Either one of these branches that I showed here or alternatively on these upper branches with Y. In that case these internal characters, ancestral and internal characters would be X. And in no way we can put this tree to have less mutations. On the lower example we see that if we rearrange a tree we can explain the observed data with less mutations. This is the needed one mutation here, meaning that this ancestral on the left internal node would be Y and this one would be X. And we would consider that the lower tree would be more parsimonous, therefore more better. This method is usually still used if you have characters such as morphological characters such as a wing shape or number of teeth or this kind of data when you have no other information about how characters actually evolve or change in the tree. On the other hand this method is too simplistic and for genomic data, so if we have let's say genes to compare and if we assume that again they all have common ancestors, we can introduce a more complex method of evaluating our trees such that it involves time and more probabilistic approach and more exact approach in inferring a tree. In order for this method to work we need to have a substitution model which models the way or the rate in which each state transforms in another state. In this case we have nucleotides but you can have something more complex like proteins, like codons, like whatever. In biology, in reconstruction mostly these three data models are used. They have all different complexities, they are all time reversible so in order for our methods to work they all have to have the same rate in both directions and also we need to introduce a concept of branch length which is a combined measure of rate of mutation on that branch and time, so we can imagine that if this is a fast evolving branch, one of them the branch would be longer or if time was longer in that period, so that means that there will be more mutation, the longer the branches we expect more substitutions to occur, also we are able to model with this if we have different parts that evolve with different speed or mutate with different speed and this model allows us to incorporate this into our model. Simplest model of evolution would be Jukes Cantor where all of these parameters here are equal and the most complex model is a general time reversible where all of these parameters are actually parameters of the model, these are three parameters so you will have to optimize on them too, so prior knowledge often is not known about the rate of substitution. So when we calculate what we actually do is take a column, so in one column we assume that all these characters in one column have a common ancestor, so we compare them in one column and then the entire matrix we have to take the joint probability distribution of entire, so we just we superimpose each column on the tree and we calculate the likelihood of this tree and we just multiply over all columns. At the end we have this, it's a value of, like with this means that with all of the parameters, three parameters like branch length substitution rates and the topology of the tree, what is the probability that this model would generate this observed data? And now when we have this as a model this we define a space and this is each topology configuration, so if we switch leaves on these trees and each parameter when we change, this defines a space and likelihood defines kind of like a surface over this space. So what our goal is we want to find the best model to explain the observed data, we need to find the tree topology and configuration of parameters on this tree that will maximize this surface, so we find the model that is best in explaining the data. And I have to mention that in this case the amount of trees, as you add more trees, as you add more species or entities on the vertical of this matrix, the amount of trees that you can possibly generate, that can possibly be generated with this set of species, grows exponentially, even more than exponentially. So you can imagine that if you have like 100 or 200 species, if you would want to check every configuration of branches, this is an infeasible problem, you cannot check every one of them and see which one has the highest likelihood and then pick this as the model. Just to show for example how we move in this space, for example we changed topology as explained and we in this example I cut this tree here, so we have two sub-trees and I re-branch it here, and this is one moving in this space of topology and ideally we would have to do all the possible combinations of these changes and all the possible combinations of branch lengths and substitution models to find the best one to explain our data. Of course we cannot do that, so we have to come up with smart algorithms to kind of help us not find the best one but kind of cope with this problem in a way. So first approaches in solving this problem are put to representative problems, algorithms, first one is neighbor journey, basically it makes a distance matrix between each entry of each species, so how distant they are from each other, so it will be a rectangular matrix and it's kind of an algorithm for clustering based on that is more adapted to problems in biology. So we just will group the closest ones together and then we'll find some kind of a midpoint that will be, so let's say for example here, these two will be closest together, it will group them together in a cluster and then it will calculate the midpoint and then for all future clustering this midpoint will be compared to other species or other nodes. Another one is a greedy search, it starts with either random or we can use for example neighbor journey to produce a starting tree for research and then from one point it calculates all possible immediate steps, so it doesn't try all combinations but from this, from this point it takes branches and tries around and then the best one it finds it moves to this point and then explores the space around it and moves to that point and then until all the neighbors of this current tree are worse than this current tree then we say we stop and we hope we found the best. But the problem with this is if you can imagine this mountain to be our likelihood function and this space to be our space of parameters and branch lengths and substitution parameters, if we start here, we just climb up to the first local optimum and we will stop there, although let's say these other peaks here are higher than this we found but for some purpose sometimes this is enough. Another approach that is actually used in phylogeny but in all other, a lot of others, other branches of engineering is genetic algorithms which try to emulate natural evolution. So I have a population of possible solutions and then they define in one time point, they define a population in that time point, that generation and then they produce offspring, for example in our case offspring could be just another point around this point and then in order to survive they compete there we have some sort of selection function that will kind of in some kind of stochastic way try to push the entire population toward better solutions. So the higher they are on this space, more likely they are to survive to the next generation. It is slower because we have to cope with more points. It has a parallel search but in some way we hope that we will avoid the problem of reaching local optimum like here, that for example some of them will with their jumps actually reach to the top. Again it's not a solution that will always give you the best possible solution but it has been shown in multiple occasions that it will actually perform better than this one. Of course if we have a super simplistic example of just one peak then this one will perform as good. And in actually my supervisor and with another collaborator in early 2000s they came up with an idea how we of consensus pruning. Consensus pruning so it's a modified genetic algorithm so we have these multiple populations that are independent as you see here for example these red ones and blue ones and in our case so this is really specific to the problem of trees if they agree so these independent populations agree on certain branches certain clades in this example they will not try to break this so when we do these kind of moves as here between trees they will not break these red branches in this example this is so-called consensus. So we agree that this is a clade and then several different populations evolve in such way that they all agree that this is a good clade then we will not try to break it which means that this will help us reach top faster because with normal genetic algorithm you still have to if you as I expected if you if you generate offspring or propositions of new trees trying all possible combinations of plucking up the branches and regrafting them on another place it can be very cumbersome so by these kind of agreements that we shouldn't touch these parts of the tree we actually can significantly reduce the space that we explore and hopefully reach the peak faster because everything I'm talking about here is very computationally expensive so if you have huge amount of amount of species and huge amount of characters this can take weeks sometimes so if there any any any improvement in speed is welcome so I talked so far about optimization and this is we call this maximum likelihood so this is the goal to find the best solution the best the best model that explains the data another approach is not really not that you know position with the first is to to we define robustness and robustness would be when we find a trade we want to be have some metric that will tell us how how good this clade is compared to other alternative clades so for example here if we group A and B or B with a so in a plate and if we group B with D this one this one could be better or this one could be better than this one but they can be very similar and if they are very similar in there in their explanatory power they don't want to know that because that would be if we come out with this clade but with this clade as our solution this one we say okay this is better one but maybe there is an alternative one that is similar not as good but it's not far from it so for example here if if tree tree tree three has likely likely could have found about 30% and tree one has like 30% we cannot be as sure this due to no data due to whatever but we want to have this this metric and this so far to achieve this the most popular methods are Bayesian statistics and it includes this allows you to include some kind of prior knowledge maybe you know something in advance that restrict your search space or your model or you know that some parameters behave in certain ways so you can incorporate this knowledge into your into your analysis and then you will get posterior distribution that is like probability of model having the data so far we're having the probability of data having the model but yeah this allows you to do that another way how we implement in metapyga is to also to repeat analysis and see how often we came to certain peaks and then include this in in the in the you know as a include this as a metric of robustness third way would be that to have so called bootstrapping so you sample some data and then this is well known statistical method of having coming to exactly this kind of metrics now for the end I will talk about my project it was a software made in order to explore the efficacy of consensus group and when he started the phd for me they decided that will they want to be more user friendly more more flexible of a software because they were frustrated with usually their command line and you need to read a manual five thousand pages to understand how it works so they they started with the idea that they should be easily portable over multiple platforms initially they had only this maximum likelihood method to find the optimum and then they said this is simple method to calculate robustness from new version that is not yet published but I worked on I implemented Bayesian inference so you can have the full Bayesian like Mr. Byron so you can have that and features that you can use nucleotides as your input data you can use amino acids and you can use codons and also you can in from the from the software you can easily exclude certain parts or partition certain parts or you can immediately outgroup has a nice user friendly interface also there is we implemented this trim algorithm which is algorithm that was developed by a group in Barcelona from Tony Goddan that will actually test your data often people put data that has a lot of noise and this is some kind of a tool that will just warn you if you have chromatic data sets so you don't come to some weird conclusions if you are alive also we implemented multiple models for from very simple JC GTR and everything in between for for amino acids also also a lot of empirical models and for codon models we put the two model two possible models for for optimization again user interface very nice also if you want you one can one can window search or you define your all your parameters in your use in your graphical interface you export a file and then you can write you know on a cluster somewhere without all of this graphical goodness just if you want to paralyze things when you receive your results you can immediately in the software don't then check the topology reroute it and then see the support values branches model you can import other trees it's not as powerful as some software that are just for tree exploring but it helps if you want quick quick overview of your results also has a very simple Bayesian method for inferring and say ancestral states in ancestral nodes so it will give you we can export this you can export this as a file with numbers but can tell you for example here it's for node 5 this is the inferred ancestral sequence and also I've implemented the codon models because now all the softwares at that time I'm not I don't know about the situation now but at that time just few of softwares actually have this because it's very very computationally burdensome so I implemented that you can run it on NVIDIA's GPUs on your if you have on it goes for I mean I see that Alice it's for codon analysis up to 20 times faster and that's it the point of my my PhD so the some kind of so you know that actually what I actually the goal of my PhD is to kind of find best method out of the box that you can use for your analysis so not so if we you have here you see that you have robustness and optimization problems and these algorithms that are used for one thing and not with different problems that are used for another for the other thing to find we to find in which situation which one is better and try to try to combine them into one and actually to to make this faster faster better so if you have any questions I invite you to send emails if you want to I don't know maybe you have some ideas what to implement I'm open for all that and if you will try software the new version is not yet out because it's still in beta and I'm yeah I'm still polishing everything but if you want to try it just send me an email distributed thank you


Mae'r gweithio yn gweithio ar hyn yn tych yn ni'n iawn i'r bwysig ffordd, ac mae'ninationg'u ei gweithio ar unrhyw ddechrau. Rhyw brydestech chi'n fyw i'r gweithio ar hynny i'r bwysig ar gyfer y newid y sycelu rhagol hefyd i'r sganddyllr sy'n cymhobl. Gwybod fynd i gywetheithio ar hyn, ac dyna'r gyfrifysgau'r perursedr bydd i'r bwysig ymgwysig sy'n cyfrifysgau'r gweithio. pan am stretchy mêo leumio enwedig wedi bod SAAD wedi gąfli gwheild— felly mae ni osbllydd gyda un gatblynu pwg All�waysuol. Mae ni osbllydd gyda'r qwmprob iddod. Prisonidio ar Cathedral Ddeogol, gallu debyg ar ti nadydd Ixa i gyda Gaer transformation i'r gyfrifiad neu y ffordd i'r blynydd sy'n hefyd yw maen nhw i weld helmeto пwaicaidd i'r drosり. A certainly rhai i g screnedig ymddî yddynt yn phi wneud the old saying, the governance of the party needs to be about transparency, openness and people should be able to question about the accounts. We agree and believe that there are legitimate questions that the Scottish public deserves to know answers to. In the interests of transparency, will Hymde Ylif Ysgwylf agree to make a statement to Parliament on the financial scandal e'n gilffing the party of government here in Scotland? Ysgrifennid yn gwybod, gael ddysgu gwaith o dashboardau i gynyddiadu gwaith i gyd yn y First Minister i gael ddysgu gwaith i gyd, i gael ddysgu gwaith i gynyddiadu gwaith i gyd yn sorteun gwneud i gyd yn gynghyd yn gynydd ei gael ddysgu gwaith i gyd. Felly, i b racisti, rydyn ni'n fwylaid i gyd y gwaith i gyd yn gerda'r eisiau i gyd. A oedd eich gwaith i gyd ddysgu gwaith i gyd ddysgu gwaith i gyd yn gweithesu I'm happy to answer the question. I know there are some, of course, serious issues for the party that I lead the SNP to address, so I'm not going to shy away from that, Presiding Officer. That's why, in my very first act as SNP leader, attending my very first national executive committee, I'm pleased that we got agreement from that committee, that it elected the body that oversees the party that is elected by our members, to our review into transparency and governance, and not only into transparency and governance review, but one that has external input, particularly in the issues of financial oversight. Of course, that is an important job and an important role for me to take forward as leader of the SNP, but let me also say that what I am doing and what the Government I lead, what we are doing collectively, is focusing relentlessly on the day job. That is why, in the first few weeks of being First Minister, I didn't just double the fuel insecurity fund, I made sure that we tripled the fuel insecurity fund. Now, I know that Douglas Ross won't want to talk about that because, of course, it lays bare the harm that the Tory cost of living crisis is doing to households up and down the country, but that's also why, in the first few weeks as First Minister, I made sure that I focused— Douglas Ross will be pleased that it was me that got interrupted for once, no doubt. That is why, in the first few weeks as First Minister, I also announced £15 million for school-age childcare, targeted towards the lowest-income households, £25 million additional, £25 million to support the just transition, additional funding to support GP practices that are in areas of highest deprivation, £25 million to be able to buy back or long-lease empty properties for the social rented sector. Those are priorities for me, the priorities of the Scottish people. Although I take my responsibility as leader of the SNP extremely seriously, I and the Government that I lead will be focused relentlessly on the priorities of the Scottish people. Douglas Ross. The first words from the First Minister when he stood up were, he was happy to answer the question and then basically refused to do so, because I was simply asking for a statement and transparency, and I do think that it is needed from the First Minister because the secrecy must end, but I'm going to move on to one of the matters of substance that the First Minister should be focusing his attention on instead of his huge distraction within the party. Last year, an SNP Government agency introduced guidelines that encouraged more lenient sentences on under 25s, even in some of the worst crimes. The Justice Secretary was just asked about this in the session before FMQs, so can I ask the First Minister, does he fully support the policy that was brought forward for consultation when he was just the Secretary? Of course, this is a very important issue indeed, and while I won't comment on individual sentencing decisions, it might be right for me to do so as First Minister, let me just clarify some issues around the sentencing guidelines, which I think are really, really important. I heard Angela Constance make these points in response to a question earlier on. Sentencing guidelines are, of course, rightly entirely the responsibility of the independent sentencing counsel. Decisions about whether to approve those guidelines are, of course, for the High Court. The new cabinet secretary for justice and home affairs has written to the chair of the sentencing counsel to discuss the important work, and that letter knows that she will discuss how the counsel plans to keep those published guidelines under review. However, it is also important that, when it comes to decisions on sentencing, not only are they rightly for the independent judiciary, but that they are evidence-based. For anybody who has read that sentencing guideline, I am assuming that Douglas Ross has done so, you can see a comprehensive guideline that is evidence-based in terms of its sentencing of young people. On that sentencing guideline, of course, notwithstanding all the good that is in there, it is very, very clear that there is no bar on imposing a custodial sentence on a young person, where, of course, judiciary consider that to be appropriate, but that must be a decision not for the First Minister, not for Government ministers, neither I would say for Opposition colleagues. It is a decision rightly for the independent judiciary. Douglas Ross. A few weeks ago, my party and almost everyone in Scotland was outraged at the case of a 13-year-old girl who was raped at a park in Dalkeith. Her attacker, Sean Hog, was found guilty of rape, but he did not go to prison. All he had to do was carry out 270 hours of unpaid work. The judge said that, if Hog had committed the crime when he was over 25, he would now be behind bars. That confirms that the problem here is the sentence of guidelines that were introduced. It is very clear that the SNP's justice system is broken, so will the First Minister fix it? Before I ask the First Minister to respond, I would remind everybody in the chamber that this is a live case, and therefore any reference there, too, should be made with extreme caution. With that caveat in place, Presiding Officer, let me also say in my reaction to that case that I understand why people have concerns, but I must go back to the central point here that sentencing decisions are, of course, rightly for the independent courts and the independent judiciary. The Lord President reminded me of that when he made some remarks on the public record when I attended the court of session to give my oath as the First Minister of Scotland. I committed to upholding the independence of the judiciary, a responsibility that I take with the utmost seriousness. I also read the very distressing account of the victim who was 30-year-old at the time, and I also heard from her family on the public statements that have been made. Everybody, frankly, would sympathise with the strong feelings of the victim. It is important to say at this stage, talking in the general—not about that specific case, of course—that 98 per cent of all those who are convicted of rape, of rape between 2018 and 2021 received a custodial sentence. It is important that we continue to give the judiciary the independence that they have. It is important to have that separation between the Government and the judiciary. In the letter that Angela Constance has sent to the sentencing council to the Lord Justice clerk, the Government would like to discuss the issues around how the sentencing guidelines are kept under review. I take the point that Douglas Ross makes—that there is clearly a public interest in that sentencing guideline. Douglas Ross. The First Minister mentioned that he had seen the comments from the victim and her family, and that this is all in the public domain and is very legitimate to raise here in the chamber. The grandfather of the victim said that, with the new ruling that they have, any person under 25 can go out and do any crime that they want, however horrendous it may be, and there is a good chance that they will get a community payback. The survivor of this rape said this. When I was told that he had been found guilty, I felt a wave of emotions. I did not know how to react. I cried with relief. Now it makes me think, why did I even bother supporting the rape in the first place? She continued, whoever is in charge of the justice system needs to sort this out. You say you care about victims like me, but how can a serial rapist receive 270 hours of community payback?  The First Minister seems to be hailing 98 per cent of people convicted of rape going to prison. It must be 100 per cent of rapists convicted of that crime going to prison. Let me repeat the words of the victim as my question to the First Minister.  Speaking in the general, I agree with the sentiment that, if somebody commits rape, they should go to jail. I believe that, but I also firmly believe that it is up to the independent judiciary, judges and those in the high court to make a decision about what the appropriate punishment is for an individual for the crime that they have committed. Let me again refer back to the sentencing guideline, which is the central issue that Douglas Ross raises with me. The guidelines make it clear that, as well as looking at issues around rehabilitation and consideration of sentencing for young people under 25, the other factors, including punishment, protection of the public and expressing strong disapproval of offending behaviour, should also be taken into account. The courts can still, even with that guideline in place, impose a custodial sentence on a young person if they consider that to be appropriate in light of all the facts. I take what has been said by the victim and her grandfather very seriously indeed. That is why we are looking to improve the justice system when it comes to particularly those individuals, particularly women, who are often the victims of sexual offences and rape. We will shortly introduce our criminal justice reform bill, which seeks to make those changes to the court system, to the justice system in order to be able to improve the experience and improve outcomes of justice for victims of sexual offences and rape. I hope that it will get support from right across the chamber. On Tuesday, Humza Yousaf tried to convince the country that he represented a fresh start. It is 16 years of command and control, financial mismanagement and a complete lack of transparency. That is not just how they govern their party, it is how they govern the country. Just one example, the on-going ferry crisis. £200 million over budget with no ferries in sight. Last week I was in the western Isles and I heard directly from people about the consequences of this failure. Cancelled ferries, meaning missed cancer appointments, lack of supplies coming in, produce not getting out and businesses going to the wall. In 2017, the then SNP Minister for Transport and the Islands said that resolving the western Isles ferry crisis was a priority. Six years on, they are still waiting and it has got worse. So can I ask the First Minister who was that incompetent transport minister and where are they now? I recognise the challenges that ferry services are. Those who rely on ferry services at island communities have suffered in the past few weeks, particularly given the Easter tourism season. Let me also speak very clearly to those island communities that we understand not just the frustration but that we are taking action to ensure that we bolster the ferry network services. That is why this Government has bought and deployed an additional vessel in the MV Lock Freezer. That is why we chartered the MV Arrow to provide additional resilience and capacity. That is why we commissioned two new vessels for Eila. That is why we commissioned two new vessels for the Little Minch routes. That is why we progressed key investments in ports and harbours. That is why we have confirmed additional revenue funding for the operation of local authority ferry services. That is why, of course, we are looking forward to the MV Alfred and providing additional funding to CalMac for the MV Alfred to provide additional resilience, not just for the next few weeks but for the next nine months. That is a very serious matter raised by Anna Sauer, but we are a Government that is taking action to ensure that we have resilience on our ferries network. That was the great example of what has become typical of this leadership in the last three weeks—comical alley. Everything is fine while the house burns down behind us. Island communities will not believe those excuses from the minister. The First Minister and his Government are totally out of touch. Six years ago, Humsley use of his transport minister made a promise to fix this, but this SNP Government has failed to get a grip and its financial mismanagement has cost us hundreds of millions of pounds, but it has also cost people on the islands dearly, too. The impact on the local economy has been devastating. One report has estimated that the loss of the luck boys' deal to Malay ferry alone cost nearly £50,000 a day. That is almost double the average annual salary on the islands. As one business put it, no ferry means no income, no jobs, no people. The businesses in UST have asked the Scottish Government to compensate them for their losses. Last year, Transport Scotland took millions of pounds in fines from CalMac because of the lack of services, so will the First Minister commit to compensating islanders and, at the very least, passed on the fines that the Government has collected from CalMac to the people affected by the crisis? I cannot say that I will look at any proposals that are suggested by anybody across the chamber, including the one that Anna Sauer just mentioned, but I completely accept and am unequivocal in saying that the Government understands and regrets any delays and disruptions that have impacted our island communities. What does not help our island communities is sound bites and really easy sound bites from Anna Sauer, not in any attempt to provide any solutions, but silly personal attacks around Comical Alley. That is not going to help those in our island communities one single bit. What will help our island communities, of course, is delivering six new major vessels to serve Scotland's ferry network by 2026. That is a priority for this Government. Let us look at the facts, because there has been disruption. I am not denying that at all, but in 2022, there were 170,000 scheduled sailings across the CHIFS network. Around 6.6 per cent of those were cancelled, and more than half of those were cancelled due to weather-related issues. Around 1.1 per cent of the total scheduled sailings were due to technical issues, so the vast majority of scheduled sailings take place when they are meant to. The ferry service network should bolster, and we will bolster in relation to its resilience. That is why I look forward to the charter of the MV Alfred coming on board in the coming days. What I will say to Anna Sauer is that I will end where I started. Any sensible suggestions from across the Opposition, across the chamber, will be listened to by the Government. The harsh reality is that island communities just do not believe them. Island communities feel completely let down, and they have heard these excuses for years. They cannot wait more years of Government failure. That is impacting the lives of islanders right now. Businesses are failing right now. Millions of pounds are being lost right now. Exports are stuck on the islands right now, and people need support right now, and that is why they need that compensation scheme. However, this is no fresh start. Humza Yousaf has served in Government for over a decade. A failed transport minister, with hundreds of millions of pounds wasted on ferries that never sailed. A failed justice secretary, with millions of pounds wasted on botched prosecutions and court delays. A failed health secretary, with over £300 million wasted on delayed discharge while people wait to get life-saving treatment, and just three weeks in, a failed First Minister bogged down in scandal, unable to lead and completely out of touch with the priorities of the people of Scotland. So can I ask the acting SNP treasurer why should Scots keep paying the price for SNP failure? Can I say once again to Annas Sarwar that we are acting now. That is why the MV Alfred, an additional vessel that we have helped to fund CalMac for, is coming on board in the next few days. That is tangible action, which will make a difference to our ferry networks right here and right now. He says that the people of Scotland do not trust us. He was in the Western Isles. Can I remind him that the Western Isles has an SNP MP and an SNP MSP, so the people of the Western Isles absolutely do trust us. Members, we need to hear the First Minister respond. He says that we have not been getting on with the job. I am afraid that people in Scotland disagree with him. When I stood here on Tuesday and announced and articulated our policy perspective, I am delighted that it got support from the SCVO. Some of the policies that I announced got support from Dr Liz Cameron, the chief executive of the Scottish chambers of commerce, from Transport Scotland, Transform Scotland, forgive me, in relation to the pilot for peak rail fares being abolished, from the Scottish Whiskey Association, from the Chartered Institute of Housing in Scotland, from the Scottish Empty Homes Partnership, from Crisis Scotland, from Reform Scotland, from the Poverty Alliance, from Stop Climate Chaos, from Parkinson's UK. That is a time for new leadership, of course, which I am delighted to bring to this Government. It is a time for a fresh start. The people of Scotland recognise that. Maybe it is time that Scottish Labour should recognise that, too. To ask the First Minister whether he will provide an update on what recent engagement the Scottish Government has had with the UK Government regarding the proposed development of the Rose Bank oil and gas field in light of the Scottish Government's draft energy strategy and just transition plan. First Minister. Licensing, exploration and production of the offshore oil and gas sector, of course, remain reserved regrettably to the UK Government. The Scottish Government is clear that unlimited extraction of fossil fuels is not consistent with our climate obligations. It is not the solution to the energy crisis, meeting our energy security needs or, indeed, ensuring a just transition for our oil and gas workers as North Sea production inevitably declines. That is why we need a new plan for Scotland's energy system. The draft energy strategy and just transition plan seeks to do that. The Scottish Government is absolutely committed to a just transition and ensuring that we take workers with us on that important journey to net zero. We will not do to the north-east what Thatcher did into mining and stealing communities right across Scotland. First Minister, for that response, while recognising that licensing is reserved, the draft energy strategy and just transition plan sets out a position that, in order to support the fastest possible and most effective just transition, there should be a presumption against new exploration for oil and gas. Since the draft plan was published, the UN Secretary General has said, our world needs climate action on all fronts, everything, everywhere, all at once, ceasing all licensing or funding of new oil and gas, stopping any expansion of existing oil and gas reserves and shifting subsidies from fossil fuels to a just energy transition. Whether it is Rosebank today or other proposals to drill tomorrow, does the First Minister agree that a just transition on a liveable planet depends on our firm commitment to a fossil fuel free future? I agree that we should all want a fossil fuel free future, and I agree on that.  One of the first things I did, I think, in my second official visit as First Minister, I went to the north-east of Scotland and I spoke to those who are absolutely committed to that just transition, particularly in the north-east. I want the north-east of Scotland to be in the net zero capital, not just of Europe, but the net zero capital of the world. I believe that it has the potential to do so. Maggie Chapman is absolutely right that, first and foremost, we must make sure that any decisions that are taken by the UK Government must be taken in relation to our climate obligations. We want the UK Government to strengthen its climate compatibility checkpoint. We have asked for tougher, more robust climate tests. Secondly, we should ensure that they align with our energy security needs. Thirdly, and that is really central, and I believe that Maggie Chapman will absolutely agree with that, we must take the workers of the north-east with us. As I have already said, we will never do to the north-east what Margaret Thatcher did, to our mining and steel communities. We will not decimate sectors. We will not leave a single worker on the scrap people. That is why I will continue to invest in the just transition and accelerate that just transition as quickly as we possibly can. First Minister, new exploration and production in the North Sea would protect over 70,000 Scottish jobs. It would help our energy security and it would have a positive impact on emissions rather than offshoring our responsibilities. Therefore, will the First Minister reexamine the plans in his threadbare energy strategy to close the North Sea, or will he continue to be dictated to by a cabal of green MSPs? Of course, that is not what is in the draft strategy. However, if we were to unleash and truly unlock the green economy, we are talking about tens of thousands of jobs over the next couple of decades. We want to take the workers of the north-east in particular with us on that journey. What a cheek that Liam Kerr stands there and talks about Scottish jobs when it comes to energy when the party that he belongs to, the UK Government, has continued to block, to delay and to dither when it comes to the Scottish cluster and the ACON project, which they have refused to give commission to and have relegated to track to. Let me say once again that the Tories can never be trusted when it comes to protecting Scottish jobs. Here in Scotland and the UK, we will need and continue to need and rely on gas for decades to come. The gas is imported in many cases from the USA, but its gas is produced with over four times the carbon emissions of Rosebank. Therefore, does the First Minister agree with me that sacrificing development of our own gas resource would not only decimate tens of thousands of highly skilled, well-paid jobs in a form of economic masochism advocated by the Wine Bar revolutionaries in the Green Party, but also make climate change worse, actually worse, not better? Before the First Minister responds, I remind all members of the requirement to treat each other with courtesy and respect. First Minister? I have a feeling, Deputy Prime Minister, that is not the first time that you have had to tell off your brother at one's suspects, but let me at some point of agreement with Fergus Ewing say that nobody in the Scottish Government, certainly not just in the Scottish Government, but also in the Green Party, has said that extraction has to stop tomorrow, because we understand that a just transition means that we have to take the workers of the north-east with us. Of course, the point is that it is a just transition. It has to be just, and that is why we believe that we must accelerate that just transition with further investment in those non-fossil fuel alternatives. I would say that independent research based on industry projections found that production in the north-east will be around a third of 2019 levels by 2035. We know that it is a declining base, and hence why we have to make sure that we are accelerating that just transition. Meanwhile, as of 2019, only 16 per cent of the oil and gas that is coming into Scotland, including imports from Norway and beyond, is consumed in Scotland. Reducing our energy consumption while ramping up our energy generation capabilities through renewables and hydrogen will mean that a net zero of Scotland will not only be less reliant on importing oil and gas, but will hopefully be a net exporter of cleaner and greener energy to the rest of the UK and beyond. To ask the First Minister, in light of his recent visit to the port of Aberdeen, what engagement has he had with the business community since taking office? Resetting the relationship with business is a core priority for this Government, and Tuesday I set out plans to agree a new deal for businesses. The introduction of a new group co-chaired by the Cabinet Secretary for the Well-being, Economy, Fair Work and Energy will explore how Government can better support our businesses and communities using all the policy levers that we have to our hands. During my visit to the port of Aberdeen, I announced £25 million, as I have already referenced, to be invested for the just transition away from oil and gas. That was the first of many meetings that I have planned as part of an extensive programme of engagement with business and industry leaders across all of Scotland's sectors to identify those priority areas of both challenge and opportunity. Later today, I will also meet the main business organisations to personally reiterate my commitment to this new working relationship and how we can deliver on our mission of a fairer, greener and indeed a growing wellbeing economy for all of Scotland's people. I thank the First Minister for his response. The Scottish Government's commitment to agree a new deal for business has received an extremely positive response from the business community, and we all agree that it is absolutely vital that we work together constructively to develop our wellbeing economy. Given the substantial pressures that many businesses are facing from rising costs and a disastrous Brexit, it is clear that urgent and sustained action is needed to maximise the support that is available to them. Can the First Minister say any more about the steps that the Scottish Government is taking to ensure that it can best support our businesses using the full policy levers that it has at its disposal? Does he agree that with full powers over our economy resting with this Parliament, we would be much better placed to support our businesses to thrive? Of course, we would. Absolutely. I can hear groans and jeers from the Scottish Conservatives. Let's read what the chairman of the OBR said about the impact of Brexit on the UK economy. He said that it was on the same magnitude as Covid, as the Covid pandemic—an energy crisis that the pandemic has had. He said, of course, in fact that the Centre for European Reform said that they found that Brexit has cost the UK a staggering £33 billion in lost trade. That is not just the opinion of the SNP-led Scottish Government. It is the opinion of those experts in the economy who are saying that Brexit has seriously impacted trade in the UK and trade here in Scotland, too. Businesses are the backbone of the economy.  That is why the new deal for business, which I articulated in our policy perspective on Tuesday, is so important. It is crucial. Through the Scottish budget, we responded to business's biggest ask and non-domestic rates by freezing the poundage in 2324. That is estimated to save rate pairs £308 million. We will continue to use the powers of devolution that we have to the absolute maximum effect to grow and transform our wellbeing economy. However, I agree that we need significantly increased policy levers to ensure that Scotland will be wealthier, fairer, greener, and that the wellbeing of our people is enhanced. Until we do that, I am afraid that the Scottish Conservatives will continue to have the levers that we can see them use to harm our people and to harm business and trade here in Scotland. Thank you, Presiding Officer. Connectivity between the port of Aberdein and the Freeport and Cromarty will be vital for the north-east economy. Will the First Minister grow a backbone, stand up to the Greens and fully dual the A96 as promised? That goes to the heart of the Conservatives' hypocrisy. The demand we go further on tackling the climate emergency, anything we do, including a review, for example, of sections of the A96, for climate compatibility, is opposed. It does not matter what the Scottish Government tries to do to ensure that we tackle the climate emergency, so we leave a cleaner planet, a sustainable planet for our future generations. The Conservatives will always, always oppose it. Let me say very clearly that we are absolutely committed, of course, to the drilling of the A9, but also to the A96, inverness to Nairn and Nairn bypass. I have said already to my good friend, Fraggus Ewing, that we will bring forward a timetable on that as soon as we possibly can. To ask the First Minister whether he will provide an update on the Scottish Government's plans for highly protected marine areas following the end of its public consultation. Our initial consultation on highly protected marine areas closed on Monday. It is only right, of course, that we do take some time to carefully consider all the responses, and there has been a substantial number of responses before we set out our next steps, as I say, especially given the strength of views that we all know have been expressed on that issue. Our seas, of course, must remain a source of prosperity for the nation, especially in those remote coastal and island communities. It is vital that those communities do help shape the creation of those areas, which is why we chose to consult very early on in this process. My officials have held over 40 meetings relating to the process. My colleague, Manny Macallan, will continue to engage directly with coastal and island communities before we decide our next steps together. To be clear, no sites have been selected. That will not begin until we have considered the consultation's feedback and until that engagement is complete. We are determined to ensure that as many voices as possible are heard in this process. Earlier this week, the First Minister said that HPMAs should not be imposed on communities that do not want them. The First Minister not one community in the Highlands and Islands wants these, not one. We all acknowledge the need to protect our marine environment, but those proposals will devastate coastal communities and threaten their very way of life, particularly the fishing sector. It is no wonder that this policy has been compared to the clearances, people cleared off the land and cleared off the sea. Given the anger that this has caused, given the widespread opposition to those plans, including from many in his own party, and given that he wants to be First Minister for the whole country, will he now scrap those plans once and for all and start again? The point is that there are no plans yet. There is a consultation. We do not have set sites. We do not have set criteria yet. What we want to do is to work with coastal communities, island communities and our fishing communities at a very early stage in the seption stage. Ultimately, I believe that there is agreement on the outcome. The outcome that we all want is the sustainable marine environment. What we want is our fishing industry and our seas to be sustainable for the future. We want that industry to continue, but we can only do that if the marine environment is sustainable. I believe that there is an agreement there. Of course, our fishing communities, island communities and coastal communities have often been at the forefront of that effort around sustainability. We want to work with them, we want to engage with them and all that is being said. I reiterate what I said on Tuesday that the Government will not impose on any community a policy that it is vehemently opposed to. My colleague Mary McAllan will engage with island communities and coastal communities and we will analyse those responses carefully. However, for all those who have expressed their opposition to highly protected marine areas, we are willing to engage, we are willing to listen and let us hope that we get to the agreed outcomes together. Does the First Minister agree that the no-take zone in Amlash Bay has had no adverse impact whatsoever and has shown that conservation can help to revitalise our fishing sector and that identifying potentially highly protected marine area sites would allow more effective direct engagement with concerned fishers and communities? Far from having any adverse impact, it has shown us the benefit for both the marine environment and the people who rely on it. I go back to that point. I think that a very good example in relation to Amlash Bay was the community that wanted that no-take zone. That goes to the central point that we will work with communities hopefully to get to the outcomes that we all agree on, which is a sustainable marine environment. Based on studies that were co-ordinated by the community group at Amlash Bay, it has been noted that, since protection commercially important species such as the King scallop and the European lobster have increased in size, they have increased in age and in density. The 2008 designation of the Lamlash Bay and no-take zone off the coast of Arran, as I said, was a result of campaigning by the local community, and that is a good model for us to take forward our work around highly protected marine areas. Earlier this week, Orkney Islands Council joined counterparts in Shetland and the Western Isles in voicing the strongest possible opposition to the Government's plans for highly protected marine areas, given the potential impact on island communities. On the same day, the First Minister announced welcome, if long overdue, U-turns on his deposit return scheme and alcohol advertising sanctions. Can I therefore urge him not to spend months defending the indefensible and confirm in light of the significant and growing opposition in coastal and island communities that his Government will now rethink its plans to arbitrarily designate 10 per cent of Scottish waters at HBMAs by 2026? Lee MacArthur, we are well aware that when I was a transport and islands minister, I introduced and brought forward island proofing, which is something that I believe in to my very core. Therefore, we will not impose on any community, island or otherwise a policy that they vehemently oppose. Let's analyse the consultation responses. Let's agree on the outcomes. I think that there is generally broad agreement on the outcome that we want to have a marine environment that is sustainable. We want to have a fishing sector that is sustainable in the long term, and of course protecting our biodiversity helps us with that outcome. I will continue to engage personally. Maireen McAllan will also engage personally. She will have no doubt travel right across the country, including to Orkney and Shetland, to meet those who have expressed concerns and together. I hope that we can get to a place where we all agree on the outcome and then of course move forward to protect our marine environment to make it more sustainable for the future. To ask the First Minister what immediate action the Scottish Government will take to improve the situation regarding ferry services across the Highlands and Islands in light of recent reports of unprecedented disruption. As I have already said in response to a question from Anna Sarwe, I recognise that that is a significant impact. That delays that disruption does have during the annual overhaul programme, and it has regrettably had on our island communities. We know that island communities of course rely on those lifeline services, not just of course individuals, but businesses, too. I am committed to investing in our ferry services. Indeed, we are going to be delivering six new major vessels to serve Scotland's ferry network by 2026, which is a priority for me and for the Government that I lead. We have already procured MV Locfisa, previously chartered the MV Arrow, and of course we look forward to shortly welcoming the MV Alfred into service, providing some additional resilience to the network. In the meantime, we will continue to press CalMac to consider all options to minimise the impact on communities and indeed businesses. I know that the Minister for Transport is engaging very closely on the issue. He has held resilience calls with CalMac, with Transport Scotland in light of the latest disruption, and he has proactively engaged directly with local stakeholders, with our operators and CMAL, on improving reliability and resilience right across the network. Rhoda Grant. The Transport Minister refused to take responsibility for the ferry crisis, and he also refused compensation payments to local businesses who are actually going to the wall because of those ferry failures. Now that Constituents in the US will have no mainland services from Sunday—that is two days' time—is the First Minister going to do the same? Or is he going to tell us what emergency provision he is going to put in place? Has he asked the MOD for help and what compensation is he going to give to businesses that will close as a result of that? I have already said in response to the question from Anasawa that we will consider the issues around compensation and what more we can do to support businesses when there is disruption, but I do not agree with the premise of our question. I know that Kevin Stewart has been directly involved and engaging with CalMac, but also with the island communities that have been affected. I go back to my response to both Anasawa and Rhoda Grant that we have the MV Alfred coming on board, I hope, within the coming days, and that will provide some further resilience to our network. However, I take the points that have been made and raised and, of course, any disruption to our ferry network is regrettable. The other point that I know that Kevin Stewart has been engaging on is that we want to ensure that we improve our communication and CalMac's communication with islanders when disruption takes place. The Scottish Government has now officially asked the UK Armed Forces to step in and provide a temporary replacement service across the Coron Narrows. While this is a Highland Council-run service, it highlights the lack of resilience and the growing crisis in Scotland's ferry network. Can the First Minister advise me if he was involved in signing off that request to the MOD and, if so, when he did that? Given the need to ensure that this kind of disruption and the severe impact that it has on local communities does not happen again, will he commit today to either he or his new transport minister visiting the area at the earliest opportunity to meet with local residents and businesses? I have just a slight correction to Jamie Halcro Johnston's question. It is our MOD, our Scottish taxpayer money, that helps to fund the MOD. It is important that, when he talks about the MOD stepping in, our assets that Scottish taxpayers help to contribute towards. That is a really important point of clarification. Of course, the Scottish Government has been as helpful. We have helped to facilitate that engagement between Highland Council. We know that the Coron ferry is its responsibility. In fact, the MOD was my colleague Ian Blackford, the MP for Ross, Skye and Lochaber, who has helped to ensure that facilitation between Highland Council, the MOD and the Scottish Government. We will do everything that we possibly can in relation to that MACA request. My understanding is that there are initial assessments that the MOD is doing. Whatever the next steps are in relation to the process that involves the Scottish Government, we will be as helpful as we possibly can. I also remind Jamie Halcro Johnston that the former Deputy First Minister announced in his final budget that the Scottish Government would provide full revenue funding to councils who run their own ferry services. Our officials are in very proactive engagement with the Highland Council about those costs. Of course, Kevin Stewart would be happy to visit the Highlands and talk to local community about the Coron ferry route. To ask the First Minister what urgent action the Scottish Government is taking to ensure that everyone who is eligible for any cancer testing and screening programme is receiving their invitation on time, in light of recent reports, that 13,000 women who were mistakenly removed from the national database are being offered an appointment for a cervical smear. I thank Beatrice Wishart for raising what is an incredibly important issue indeed. The national audit of the cervical screening programme is under way. It is a result of an incident that was brought to our attention in 2021, where a small number of women were incorrectly excluded from the cervical screening programme after having sub-total hysterectomies. At this final stage of the audit, it is precautionary that it follows an initial audit in 2020 of those women who were considered to be at the highest risk of being wrongly excluded. No cervical cancers were detected as part of that audit, and the risk to participants in that audit is very low. The actual number of patients who need to be reinstated to the screening programme obviously will not be known until that audit is complete and all affected individuals are contacted. Funding has been made available, particularly to GP practices, to ensure that they can absorb any increase in demand. I thank the First Minister for that answer, and I recognise the complexity of the case. We were talking about a statistically small number, but every number is a person who will no doubt be concerned when they receive a letter. Can the First Minister assure those with concerns that measures are in place to ensure that similar errors are not repeated, that all those affected will be contacted as swiftly as possible? Can he indicate what work is under way to improve access to screening, including the introduction of self-sampling, to ensure that this news does not further impact uptake? Beatrice Wishart is absolutely right, although the numbers may be small. If you receive that letter, I can imagine the impact and the concern that you have. That is why I was very keen to reiterate that the women who were called in the first audit were the ones who were most at risk. If you are receiving a letter or are being asked to come back in for screening, there is low risk, but there is still risk. That will be a concern for those who receive the call-up as part of the audit. Beatrice Wishart is also right to ask what we have done in relation to ensure that this error does not occur again, and that is an error that has occurred. I am afraid that we have known the system for many years. We have made improvements to the IT systems in relation to the cervical cancer screening programme. We have also improved the record-keeping process. All 14 territorial boards have taken action in relation to their audit activities. We expect the audit to be fully completed in the next 12 months. We have started with those at the highest risk. In relation to cervical cancer, she has already mentioned some of the initiatives that we are taking forward. We are also seeking to do more in relation to mobile screening units, which we know are particularly important in rural, remote and island communities. Beatrice Wishart raises an important point about the fact that we need to make sure that screening of all cancer, cervical cancer included, is accessible to as many people as possible. Thank you, and we will now move briefly to general and constituency supplementaries. I call Fiona Hyslund. The First Minister will be aware of an article in this morning's telegraph by Conservative peer, David Frost, which proposes to reduce and remove powers of devolution and undermines this Parliament. Can I ask the First Minister how his Government intends to defend the powers of this Scottish Parliament from unelected Tories at Westminster, intent on dismantling devolution? Does he agree that it is for all MSPs, from all parties, to defend this Parliament from an attack on democracy? Lord Frost's unelected Tory peer gave the game away. He said the quiet bit out loud. He said what every single Scottish Conservative really thinks. He said—and I will quote him, Presiding Officer— "...not only must no more powers be devolved to Scotland, it is time to reverse that process." He said that ministers should make it clear that if re-elected, they will review and roll back some of the currently devolved powers. It is hardly a surprise that the party that didn't support the Scottish Parliament now wants to dismantle the Scottish Parliament, but let me be abundantly clear whether it is on the section 35 veto, whether it is there in ability to grant an exemption under the IMA, under the internal market act, whether it is the fact that it wants to curtail our excellent international development work or external engagement with the SNP-led Scottish Government, we will always defend our democracy and we will always defend the voice and the will of the Scottish people. The First Minister will be aware of the NSPCC Scotland report, keeping the promise to infants 0 to 3. The report states that, in Scotland, we have a baby blind spot in the care system. It also states that, despite the youngest children in Scotland being the most vulnerable to harm, the 0 to 3 age group can often be overlooked, which is shocking, especially when a quarter of all child protection orders are for infants under 20 days old. It makes reference to the need to improve support and redesign of services to keep the promise. Given the public commitments made by the previous First Minister, what will the current First Minister do to ensure that the baby blind spot in Scotland is removed once and for all? That is a very important issue that was raised by Ross McCall indeed. She is right to scrutinise what the Government is going to be doing to keep the promise. I made an unapologetic and unequivocal commitment in relation to this Government's determination to keep the promise. I, of course, have appointed a minister who has responsibility for keeping the promise, and Natalie Dawn will report directly to me as First Minister on that particular issue. We will lay out, as a Government, in detail what we can do for care experience young people. There, of course, has been some legislation passed by this Parliament on issues such as, for example, sibling separation. However, I heard from care experience young people in particular that we need to go further in terms of implementation of that legislation on the ground, and Ross McCall rightly raises the issue of the baby blind spot, as it is referred to by NSPCC. Of course, that is another issue that I am determined that we do more on. I will give, as I say, an unequivocal commitment to ensuring that this Government keeps the promise, not just for babies and young people. That is important, but, of course, care experience is lifelong. Scottish hospices are facing a perfect storm of rising staff costs, increased energy and running costs and a tough fundraising environment. They need urgent funding to match the NHS pay uplift so that they can offer their staff the fair wage that they deserve. Hospice UK met the First Minister in his old role as health secretary some five weeks ago, but all they have had since are holding responses. Time is running out, and hospices will need to make decisions in order to sustain their services. Will the First Minister act swiftly, indeed today, and provide hospices with the additional funding that they so urgently need? We are investing a record £19 billion in a health and social care system this year that has only been possible because of the progressive taxation that we have brought forward as a Government. I will speak, of course, with the Cabinet Secretary for Health and Social Care to see what more we can possibly do, what funding we are able to provide, but every single penny of our funding has been allocated. I understand that the issues raised by Jackie Baillie on behalf of hospices UK are very important. I value the work that hospices do right across the country. I have had personal experience when I lost an uncle to pancreatic cancer, forgive me, many years ago. I take the issues that Jackie Baillie raised very seriously, indeed, and we will look to see whatever we can do to support the excellent work that our hospices do right across the country. That concludes First Minister's questions. The next item of business is a member's business debate in the name of Foisal Chowdhury, and there will now be a short suspension to allow those leaving the Chamber and Public Gallery to do so before the debate starts. Thank you.


You do not receive a baby Holy Spirit at salvation. You do not receive a portion of the Holy Spirit at salvation for how can the eternal be divided into portions? No, the moment you are born again, the Holy Spirit in the fullness of His presence and power comes to dwell in you. The very same which rested on the Christ, the very same which was active in the ministries of the disciples, the very same that was active in the ministry of Paul the apostle, the very same that stirred David to write the Psalms, that stirred Solomon to write the Proverbs, that moved the prophets of old to declare the oracles of God, that revealed the coming of the Messiah, the very same Holy Spirit who in the book of Genesis hovered above the face of the deep. This precious Holy Spirit dwells in you and I.